Showing papers in "Cell Cycle in 2023"

Metformin attenuates multiple myeloma cell proliferation and encourages apoptosis by suppressing METTL3-mediated m6A methylation of THRAP3, RBM25, and USP4

Abstract: ABSTRACT Based on the results of epidemiological and preclinical studies, metformin can improve the prognosis of patients with malignant tumors. Studies have confirmed that metformin inhibits multiple myeloma (MM) cell proliferation and promotes apoptosis. Nevertheless, the specific mechanism remains to be elucidated. MM cells were intervened with different doses of metformin to detect cell proliferation and apoptosis. Western blotting and RT-qPCR were employed to assess the expression of METTL3, METTL14, WTAP, FTO, and ALKBH5 after metformin intervention. The microarray dataset GSE29023 was retrieved from the Gene Expression Omnibus (GEO) database and calculated using the R language (limma package) to authenticate differentially expressed genes (DEGs). The database for annotation, visualization, and integrated discovery (David) was applied for GO annotation analysis of DEGs. Subsequently, the string database and Cytoscape software were applied to construct protein–protein interaction (PPI) and DEM hub gene networks. Bioinformatics analysis and MeRIP were applied to predict and test METTL3-mediated m6A levels on mRNA of THRAP3, RBM25, and USP4 in METTL3 knocked-down cells. Then rescue experiments were performed to explore effects of METTL3 and THRAP3, RBM25, or USP4 on cell proliferation and apoptosis. The effect on MM cell xenograft tumor growth was observed by injection of metformin or/and overexpression of METTL3 in in vivo experiments. Metformin decreased cell proliferation and encouraged cell apoptosis in a dose-dependent manner. Global m6A modification was elevated in MM cells compared to normal cells, which was counteracted by metformin treatment. Furthermore, THRAP3, RBM25, and USP4 were identified as possible candidate genes for metformin treatment by GSE29023 data mining. METTL3 interference impaired m6A modification on mRNA of THRAP3, RBM25, and USP4 as well as expression levels. The mRNA stability and expression of THRAP3, RBM25, and USP4 was decreased after metformin treatment, which was reversed by METTL3 overexpression. THRAP3, RBM25 or USP4 knockdown reversed the assistance of METTL3 overexpression on the malignant behavior of MM cells. Finally, upregulation of METTL3 was shown to exert facilitative effects on xenograft tumor growth by blocking metformin injection. The present study demonstrates that metformin can repress the expression of THRAP3, RBM25, and USP4 by inhibiting METTL3-mediated m6A modification, which in turn hamper cell proliferation and promotes cell apoptosis. Abbreviations: multiple myeloma (MM), Gene Expression Omnibus (GEO), differentially expressed genes (DEGs), database for annotation, visualization and integrated discovery (David), protein–protein interaction (PPI), epithelial‑mesenchymal transition (EMT), methyltransferase like 3 (METTL3), methyltransferase like 14 (METTL14), wilms tumor 1-associated protein (WTAP), methyltransferase like 16 (METTL16), acute myeloid leukemia (AML), non-small lung cancer (NSCLC), glioma stem cells (GSCs), normal bone marrow-derived plasma cells (nPCs), false discovery rate (FDR), biological process (BP), optical density (OD), horseradish peroxidase (HRP), M6A RNA immunoprecipitation assay (MeRIP).

Natural compounds regulate the PI3K/Akt/GSK3β pathway in myocardial ischemia-reperfusion injury

Abstract: ABSTRACT The PI3K/Akt/GSK3β pathway is crucial in regulating cardiomyocyte growth and survival. It has been shown that activation of this pathway alleviates the negative impact of ischemia-reperfusion. Glycogen synthase kinase-3 (GSK3β) induces apoptosis through stimulation of transcription factors, and its phosphorylation has been suggested as a new therapeutic target for myocardial ischemia-reperfusion injury (MIRI). GSK3β regulatory role is mediated by the reperfusion injury salvage kinase (RISK) pathway, and its inhibition by Akt activation blocks mitochondrial permeability transition pore (mPTP) opening and enhances myocardial survival. The present article discusses the involvement of the PI3K/Akt/GSK3β pathway in cardioprotective effects of natural products against MIRI. Abbreviations: Akt: protein kinase B; AMPK: AMP-activated protein kinase; ATP: adenosine triphosphate; Bad: bcl2-associated agonist of cell death; Bax: bcl2-associated x protein; Bcl-2: B-cell lymphoma 2; CK-MB: Creatine kinase-MB; CRP: C-reactive-protein; cTnI: cardiac troponin I; EGCG: Epigallocatechin-3-gallate; Enos: endothelial nitric oxide synthase; ER: endoplasmic reticulum; ERK ½: extracellular signal‑regulated protein kinase ½; GSK3β: glycogen synthase kinase-3; GSRd: Ginsenoside Rd; GSH: glutathione; GSSG: glutathione disulfide; HO-1: heme oxygenase-1; HR: hypoxia/reoxygenation; HSYA: Hydroxysafflor Yellow A; ICAM-1: Intercellular Adhesion Molecule 1; IKK-b: IκB kinase; IL: interleukin; IPoC: Ischemic postconditioning; IRI: ischemia-reperfusion injury; JNK: c-Jun N-terminal kinase; Keap1: kelch-like ECH-associated protein- 1; LDH: lactate dehydrogenase; LVEDP: left ventricular end diastolic pressure; LVP: left ventricle pressure; LVSP: left ventricular systolic pressure; MAPK: mitogen-activated protein kinase; MDA: malondialdehyde; MIRI: myocardial ischemia-reperfusion injury; MnSOD: manganese superoxide dismutase; mPTP: mitochondrial permeability transition pore; mtHKII: mitochondria-bound hexokinase II; Nrf-1: nuclear respiratory factor 1; Nrf2: nuclear factor erythroid 2-related factor; NO: nitric oxide; PGC-1α: peroxisome proliferator‑activated receptor γ coactivator‑1α; PI3K: phosphoinositide 3-kinases; RISK: reperfusion injury salvage kinase; ROS: reactive oxygen species; RSV: Resveratrol; SOD: superoxide dismutase; TFAM: transcription factor A mitochondrial; TNF-α: tumor necrosis factor-alpha; VEGF-B: vascular endothelial growth factor B

Phosphorylation of the prolyl isomerase Cyclophilin A regulates its localisation and release from the centrosome during mitosis

Abstract: ABSTRACT The centrosome acts as a protein platform from which proteins are deployed to function throughout the cell cycle. Previously, we have shown that the prolyl isomerase Cyclophilin A (CypA) localizes to the centrosome in interphase and re-localizes to the midbody during mitosis where it functions in cytokinesis. In this study, investigation of CypA by SDS-PAGE during the cell cycle reveals that it undergoes a mobility shift during mitosis, indicative of a post-translational modification, which may correlate with its subcellular re-localization. Due to the lack of a phospho-specific antibody, we used site-directed mutagenesis to demonstrate that the previously identified serine 77 phosphorylation site within CypA is important for control of CypA centrosome localization. Furthermore, CypA is shown to interact with the mitotic NIMA-related kinase 2 (Nek2) during interphase and mitosis, while also interacting with the Nek2-antagonist PP1 during interphase but not during mitosis, suggesting a potential role for the Nek2-PP1 complex in CypA phospho-regulation. In support of this, Nek2 is capable of phosphorylating CypA in vitro. Overall, this work reveals that phosphorylation of CypA at serine 77 is important for its release from the centrosome during mitosis and may be regulated by the activity of Nek2 and PP1 during the cell cycle.

Identification and validation of a cellular senescence-related lncRNA signature for prognostic prediction in patients with multiple myeloma

Abstract: ABSTRACT Multiple myeloma (MM) is the second most common hematologic malignancy, which primarily occurs in the elderly. Cellular senescence is considered to be closely associated with the occurrence and progression of malignant tumors including MM, and lncRNA can mediate the process of cellular senescence by regulating key signaling pathways such as p53/p21 and p16/RB. However, the role of cellular senescence related lncRNAs (CSRLs) in MM development has never been reported. Herein, we identified 11 CSRLs (AC004918.5, AC103858.1, AC245100.4, ACBD3-AS1, AL441992.2, ATP2A1-AS1, CCDC18-AS1, LINC00996, TMEM161B-AS1, RP11-706O15.1, and SMURF2P1) to build the CSRLs risk model, which was confirmed to be highly associated with overall survival (OS) of MM patients. We further demonstrated the strong prognostic value of the risk model in MM patients receiving different regimens, especially for those with three-drug combination of bortezomib, lenalidomide, and dexamethasone (VRd) as first-line therapy. Not only that, our risk model also excels in predicting the OS of MM patients at 1, 2, and 3 years. In order to verify the function of these CSRLs in MM, we selected the lncRNA ATP2A1-AS1 which presented the largest expression difference between high-risk groups and low-risk groups for subsequent analysis and validation. Finally, we found that down-regulation of ATP2A1-AS1 can promote cellular senescence in MM cell lines. In conclusion, the CSRLs risk model established in present study provides a novel and more accurate method for predicting MM patients’ prognosis and identifies a new target for MM therapeutic intervention.

Genetic variants underlying spermatogenic arrests in men with non-obstructive azoospermia

Abstract: ABSTRACT Spermatogenic arrest is a severe form of non-obstructive azoospermia (NOA), which occurs in 10–15% of infertile men. Interruption in spermatogenic progression at premeiotic, meiotic, or postmeiotic stage can lead to arrest in men with NOA. Recent studies have intensively focused on defining genetic variants underlying these spermatogenic arrests by making genome/exome sequencing. A number of variants were discovered in the genes involving in mitosis, meiosis, germline differentiation and other basic cellular events. Herein, defined variants in NOA cases with spermatogenic arrests and created knockout mouse models for the related genes are comprehensively reviewed. Also, importance of gene panel-based screening for NOA cases was discussed. Screening common variants in these infertile men with spermatogenic arrests may contribute to elucidating the molecular background and designing novel treatment strategies.

Statement of Retraction: LncRNA CASC11 promoted gastric cancer cell proliferation, migration and invasion in vitro by regulating cell cycle pathway.

Abstract: This article refers to:RETRACTED ARTICLE: LncRNA CASC11 promoted gastric cancer cell proliferation, migration and invasion in vitro by regulating cell cycle pathway

Ultraviolet B radiation induces oxidative stress and apoptosis in human lens epithelium cells by activating NF-κB signaling to down-regulate sodium vitamin C transporter 2 (SVCT2) expression

Abstract: ABSTRACT Ultraviolet B (UVB) exposure is reported to cause cataract formation by inducing excessive reactive oxygen species (ROS) and apoptosis in human lens epithelial cells (HLECs). Sodium-dependent Vitamin C transports-2 (SVCT2) is a ascorbic acid (AsA) transporter for that can protect cells and tissues from oxidative stress. Here, we focus on the functional characterization and mechanism analysis of SVCT2 in UVB-treated HLECs. The results showed a significant reduction of SVCT2 expression in HLECs treated with UVB. SVCT2 abated apoptosis and Bax expression and increased Bcl-2 expression. Moreover, SVCT2 decreased ROS accumulation and MDA level, but increased the activities of antioxidant enzymes (SOD and GSH-PX). NF-κB inhibitor (PDTC) alleviated ROS production and apoptosis, and promoted SVCT2 expression in UVB-treated HLECs. Additionally, ROS inhibitor (NAC) suppressed oxidative stress, apoptosis, and induced SVCT2 expression in UVB-treated HLECs, while these effects were significantly abated due to the activation of NF-κB signaling. Furthermore, SVCT2 facilitated 14C-AsA absorption in UVB-treated HLECs. Together, our findings demonstrated that UVB exposure-induced ROS generation, which further activated NF-κB signaling to down-regulate SVCT2 expression in HLECs. Then, downregulated SVCT2 promoted ROS accumulation and induced apoptosis by decreasing AsA uptake. Our data reveal a novel NF-κB/SVCT2/AsA regulatory pathway and suggest the therapeutic potential of SVCT2 in UVB-induced cataract.

Statement of Retraction: Silencing of EPCAM suppresses hepatic fibrosis and hepatic stellate cell proliferation in mice with alcoholic hepatitis via the PI3K/Akt/mTOR signaling pathway

Abstract: suppresses

Statement of Retraction: Down-regulated lncRNA TP73-AS1 reduces radioresistance in hepatocellular carcinoma via the PTEN/Akt signaling pathway.

Abstract: This article refers to:RETRACTED ARTICLE: Down-regulated lncRNA TP73-AS1 reduces radioresistance in hepatocellular carcinoma via the PTEN/Akt signaling pathway

Effects and mechanisms of trifluridine alone or in combination with cryptotanshinone in inhibiting malignant biological behavior of gastric cancer

Abstract: ABSTRACT Background The incidence of gastric cancer (GC) ranks fourth among all malignant tumors worldwide, and the fatality rate ranks second among all malignant tumors. Several Chinese traditional medicines have been used in the treatment of advanced gastric cancer. This study aims to investigate the effect of combinational use of natural product cryptotanshinone (CTS) with anti-cancer drug trifluorothymidine (FTD) in GC. Methods Cell Counting Kit-8 assay was used to detect the inhibitory effect of the combinational or separate use of FTD and CTS on the growth of HGC-27 and AGS GC cells. The combined index of FTD and CTS was calculated using CompuSyn software. To understand the mechanism, we applied flow cytometry to study the cell cycle and cell apoptosis after treatment. We also investigated the amount of FTD incorporated into the DNA by immunofluorescence assay. The expression of relevant proteins was monitored using western blot. Furthermore, the effect of using TAS-102 in combination with CTS was studied in xenograft tumor nude mice model. Results FTD and CTS inhibited the growth of GC cells in a dose-dependent manner, respectively. They both exhibited low to sub-micromolar potency in HGC-27 and AGS cells. The combination of FTD and CTS showed synergistic anticancer effect in HGC-27 cells and AGS cells. Our mechanism studies indicate that FTD could block HGC-27 cells at G2/M phase, while CTS could block HGC-27 cells at G1/G0 phase, while FTD combined with CTS could mainly block HGC-27 cells at G2 phase. FTD in combination with CTS significantly increased the apoptosis of HGC-27 cells. We observed that CTS treatment increased the incorporation of FTD into the DNA HGC-27 cell. FTD treatment activated STAT3 phosphorylation in HGC-27 cells, while CTS treatment down-regulated the concentration of p-STAT3. Interestingly, the combination of CTS and FTD reduced STAT3 phosphorylation induced by FTD. In the in vivo experiments, we observed that the combination of TAS-102 with CTS was significantly more potent than TAS-102 on tumor growth inhibition. Conclusions FTD combined with CTS has a synergistic anti-gastric cancer effect as shown by in vitro and in vivo experiments, and the combined treatment of FTD and CTS will be a promising treatment option for advanced gastric cancer.

SQSTM1 facilitates oocyte maturation through inducing ACLY degradation mediated by selective autophagy

Abstract: ABSTRACT Selective autophagy specifically eliminates certain intracellular substrates through the autophagy pathway. Organelles and aggregation-prone proteins can be degraded through the autophagy receptor protein SQSTM1/p62, which renders them a promising therapeutic approach against infertility. He et al. demonstrate that blocking of autophagy in cumulus granulosa cells can directly attenuate citrate levels and in turn affect oocyte maturation quality. Further findings show that SQSTM1 connects K63-polyubiquitinated ACLY (ATP citrate lyase) during the process of selective autophagic degradation, which further compromises the homeostasis of citrate. Therefore, the quality of oocyte meiotic maturation can be evaluated by the levels of selective autophagy in cumulus granulosa cells.

Abnormal regulation of miR-29b-ID1 signaling is involved in the process of decitabine resistance in leukemia cells

Abstract: ABSTRACT Decitabine (DAC) is an inhibitor of DNA methyltransferase used to treat leukemia, but primary or secondary resistance to DAC may develop during therapy. The mechanisms related to DAC resistance remain poorly understood. In this study, we find that miR-29b expression was decreased in various leukemia cell lines and AML patients and was associated with poor prognosis. In DAC-sensitive cells, miR-29b inhibited cell growth, promoted apoptosis, and increased the sensitivity to DAC. Similarly, it exerted anti-leukemic effects in DAC-resistant cells. When the miR-29b promoter in DAC-resistant cells was demethylated, its expression was not up-regulated. Furthermore, the expression of ID1, one of the target genes of miR-29b, was down-regulated in miR-29b transfected leukemic cells. ID1 promoted cell growth, inhibited cell apoptosis, and decreased DAC sensitivity in leukemic cells in vitro and in vivo. ID1 was down-regulated in DAC-sensitive cells treated with DAC, while it was up-regulated in DAC-resistant cells. Interestingly, the ID1 promoter region was completely unmethylated in both DAC-resistant cells and sensitive cells before DAC treatment. The growth inhibition, increased DAC sensitivity, and apoptosis induced by miR-29b can be eliminated by increasing ID1 expression. These results suggested that DAC regulates ID1 expression by acting on miR-29b. Abnormal ID1 expression of ID1 that is methylation independent and induced by miR-29b may be involved in the process of leukemia cells acquiring DAC resistance.

MiR-17- 5p/RRM2 regulated gemcitabine resistance in lung cancer A549 cells

Abstract: ABSTRACT The main objective of this study is to investigate the regulatory roles of the miR-17-5p/RRM2 axis in A549/G+ cells’ gemcitabine resistance. The cell viability was determined using CCK8 and clonogenic assays. Gene expression level analysis by RT-qPCR and Western blotting. Cell cycle analysis by flow cytometry. The dual luciferase activity assay was used to verify the target gene of miR-17-5p. In gemcitabine-resistant cell line A549G+, the drug resistance decreased after up-regulation of MiR-17-5p expression. The proportion of cell cycle G1 phase increased, and the S phase decreased. The expression level of cell cycle-related proteins CCNE1, CCNA2, and P21 decreased. The opposite results emerged after the down-regulation of MiR-17-5p expression in gemcitabine-sensitive cell line A549G–. The expression levels of PTEN and PIK3 in A549G+ cells were higher than in A549G-cells, but p-PTEN was lower than that in A549G–. After up-regulating the expression of MiR-17-5p in A549G+, the expression levels of p-PTEN increased, and the expression level of p-AKT decreased. After down-regulating miR-17-5p expression, the opposite results emerged. The dual-luciferase reporter assay and restorative experiments proved that RRM2 is one of the target genes for MiR-17-5p. Our results suggested that the miR-17-5p/RRM2 axis could adjust gemcitabine resistance in A549 cells, and the p-PTEN/PI3K/AKT signal pathway might be involved in this regulatory mechanism.

NPCs and APBs: two HUBs of non-canonical homology-based recombination at telomeres?

Abstract: ABSTRACT Apart from a few rare exceptions, the maintenance of functional telomeres by recombination-based mechanisms is restricted to accidental and/or pathological situations. Originally described in the yeast S. cerevisiae, this mode of telomere repair has gained interest with the discovery of telomerase negative cancers that use alternative lengthening of telomeres (ALT cancer) dependent on homologous recombination. In both yeast and humans, it has been shown that recombination at telomeres is spatially regulated and occurs preferentially at the nuclear pore complexes (NPCs) in yeast and at ALT-associated promyelocytic leukemia nuclear bodies (APBs) in human cells. Here, we discuss the potential relationships between these two membrane-less structures and their role in enabling unconventional recombination pathways.

Statement of Retraction: Upregulation of microRNA-576-5p protects from steroid-induced avascular necrosis of the femoral head by suppressing ANXA2

Abstract: This article refers to:RETRACTED ARTICLE: Upregulation of microRNA-576-5p protects from steroid-induced avascular necrosis of the femoral head by suppressing ANXA2

p18INK4C and BRCA1 inhibit follicular cell proliferation and dedifferentiation in thyroid cancer

Abstract: ABSTRACT Only 3% of thyroid cancers are medullary thyroid carcinomas (MTCs), the rest are follicular epithelial cell derived non-MTCs (NMTCs). A dysfunctional INK4-CDK4-RB pathway is detected in most of NMTCs. DNA repair defects and genome instability are associated with NMTC dedifferentiation and aggressiveness. Whether inactivation of the INK4-CDK4-RB pathway induces NMTCs and how differentiation of NMTC cells is controlled remain elusive. In this study, we generated p18Ink4c and Brca1 singly and doubly deficient mice as well as p16Ink4a and Brca1 singly and doubly deficient mice. By using these mice and human thyroid carcinoma cell lines, we discovered that loss of p18Ink4c, not p16Ink4a, in mice stimulated follicular cell proliferation and induced NMTCs. Depletion of Brca1 alone or both p16Ink4a and Brca1 did not induce thyroid tumor. Depletion of Brca1 in p18Ink4c null mice results in poorly differentiated and aggressive NMTCs with epithelial-mesenchymal transition (EMT) features and enhanced DNA damage. Knockdown of BRCA1 in thyroid carcinoma cells activated EMT and promoted tumorigenesis whereas overexpression of BRCA1 inhibited EMT. BRCA1 and EMT marker expression were inversely related in human thyroid cancers. Our finding, for the first time, demonstrates that inactivation of INK4-CDK4-RB pathway induces NMTCs and that Brca1 deficiency promotes dedifferentiation of NMTC cells. These results suggest that BRCA1 and p18INK4C collaboratively suppress thyroid tumorigenesis and progression and CDK4 inhibitors will be effective for treatment of INK4-inactivated or cyclin D-overexpressed thyroid carcinomas.

Statement of Retraction: Silencing of long noncoding RNA SBF2-AS1 inhibits proliferation, migration and invasion and contributes to apoptosis in osteosarcoma cells by upregulating microRNA-30a to suppress FOXA1 expression

Abstract: This article refers to:RETRACTED ARTICLE: Silencing of long noncoding RNA SBF2-AS1 inhibits proliferation, migration and invasion and contributes to apoptosis in osteosarcoma cells by upregulating microRNA-30a to suppress FOXA1 expression

Necroptosis in the pathophysiology of preeclampsia.

Abstract: Necroptosis is a newly-identified form of gene-regulated cell necrosis that is increasingly considered to be a pathway associated with human pathophysiological conditions. Cells undergoing necroptosis exhibit necrotic phenotypes, including disruption of the plasma membrane integrity, organelle swelling, and cytolysis. Accumulating evidence suggests that trophoblast necroptosis plays a complex role in preeclampsia (PE). However, the exact pathogenesis remains unclear. Its unique mechanisms of action in various diseases are expected to provide prospects for the treatment of PE. Therefore, it is necessary to further explore its molecular mechanism in PE in order to identify potential therapeutic options. This review examines the current knowledge regarding the role and mechanisms of necroptosis in PE and provides a theoretical basis for new therapeutic targets for PE.

A nonsteroidal anti-inflammatory drug, zaltoprofen, inhibits the growth of extraskeletal chondrosarcoma cells by inducing PPARγ, p21, p27, and p53

Abstract: Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and master transcription factor of adipogenesis-related genes, and has been reported as an antitumor target for chondrosarcomas. Herein, we show that the nonsteroidal anti-inflammatory drug, zaltoprofen, induces the expression of PPARγ at the mRNA and protein levels, following the induction of PPARγ-activating factors, such as Krox20, C/EBPβ, and C/EBPα, in human extraskeletal chondrosarcoma H-EMC-SS cells. Upregulation of the cell cycle checkpoint proteins, p21, p27, and p53, was observed upon treatment of H-EMC-SS cells with zaltoprofen, which probably resulted in the inhibition of proliferation of these cells observed in vitro. Zaltoprofen treatment inhibited tumor growth, induced tumor cell apoptosis, and was well tolerated in a mouse model of extraskeletal myxoid chondrosarcoma. Our results provide mechanistic insights into the therapeutic effect of zaltoprofen that should promote further studies on the rational use of this drug for the effective treatment of sarcomas.

Statement of Retraction: Long non-coding RNA GAS5 sensitizes renal cell carcinoma to sorafenib via miR-21/SOX5 pathway

Abstract: This article refers to:RETRACTED ARTICLE: Long non-coding RNA GAS5 sensitizes renal cell carcinoma to sorafenib via miR-21/SOX5 pathway

Statement of Retraction: The Lnc LINC00461/miR-30a-5p facilitates progression and malignancy in non-small cell lung cancer via regulating ZEB2

Abstract: This article refers to:RETRACTED ARTICLE: The Lnc LINC00461/miR-30a-5p facilitates progression and malignancy in non-small cell lung cancer via regulating ZEB2

Comprehensive analysis of the prognostic value and biological function of TDG in hepatocellular carcinoma

Abstract: ABSTRACT Epigenetics plays an important role in the malignant progression of tumors, in which DNA methylation can alter genetic performance without altering the DNA sequence. As a key regulator demethylation, thymine-DNA glycosylase (TDG) has been reported to participate in malignant progression of multiple tumors. In this study, we demonstrate that TDG is highly expressed in hepatocellular carcinoma (HCC) and its high expression is closely related to the poor prognosis of patients. Decreasing TDG expression can significantly inhibit the malignant biological behavior of HCC cells. ABL proto-oncogene 1(ABL1) was identified as a downstream gene regulated by TDG demethylation. In addition, TDG can affect the Hippo signaling pathway through ABL1 to regulate HCC cell proliferation, apoptosis, invasion and migration. Overall, our study demonstrated that TDG reduces DNA methylation of ABL1, increases ABL1 protein expression, and affects the Hippo signaling pathway to regulate the malignant progression of HCC.

Statement of Retraction: Downregulation of long noncoding RNA CRNDE suppresses drug resistance of liver cancer cells by increasing microRNA-33a expression and decreasing HMGA2 expression.

Abstract: This article refers to:RETRACTED ARTICLE: Downregulation of long noncoding RNA CRNDE suppresses drug resistance of liver cancer cells by increasing microRNA-33a expression and decreasing HMGA2 expression

Statement of Retraction: Long noncoding RNA LINC00520 accelerates progression of papillary thyroid carcinoma by serving as a competing endogenous RNA of microRNA-577 to increase Sphk2 expression

Abstract: This article refers to:RETRACTED ARTICLE: Long noncoding RNA LINC00520 accelerates progression of papillary thyroid carcinoma by serving as a competing endogenous RNA of microRNA-577 to increase Sphk2 expression

Progress in epigenetic regulation of milk synthesis, with particular emphasis on mRNA regulation and DNA methylation.

Abstract: Inadequate milk secretion and a lack of nutrients in humans and mammals are serious problems. It is of great significance to clarify the mechanisms of milk synthesis and treatment methods. Epigenetic modification, represented by RNA methylation, is an important way of gene expression regulation that profoundly affects human gene expression and participates in various physiological and pathological mechanisms. Epigenetic disorders also have an important impact on the production and secretion of milk. This review systematically summarized the research results of epigenetics in the process of lactation in PubMed, Web of Science, NSTL, and other databases and reviewed the effects of epigenetics on human and mammalian lactation, including miRNAs, circRNAs, lncRNAs, DNA methylations, and RNA methylations. The abnormal expression of miRNAs was closely related to the synthesis and secretion of milk fat, milk protein, and other nutrients in the milk of cattle, sheep, and other mammals. MiRNAs are also involved in the synthesis of human milk and the secretion of nutrients. CircRNAs and lncRNAs mainly target miRNAs and regulate the synthesis of nutrients in milk by ceRNA mechanisms. The abnormal expression of DNA and RNA methylation also has an important impact on milk synthesis. Epigenetic modification has the potential to regulate the milk synthesis of breast epithelial cells. Analyzing the mechanisms of human and mammalian milk secretion deficiency and nutrient deficiency from the perspective of epigenetics will provide a new perspective for the treatment of postpartum milk deficiency in pregnant women and mammalian milk secretion deficiency.

RING finger gene 180 inhibits osteosarcoma progression through regulating chromobox homolog 4 ubiquitination

Abstract: ABSTRACT Osteosarcoma (OS) is still the most common malignant bone tumor whose etiology remains largely unclear. Here, we aimed to investigate the role of a novel E3 ubiquitin ligase RING finger gene 180 (RNF180) in OS progression. RNF180 was significantly down-regulated in both OS tissues and cell lines. We up-regulated RNF180 using over-expression vector and knocked down RNF180 using specific short hairpin RNAs in OS cell lines. RNF180 over-expression inhibited the viability and proliferation yet promoted apoptosis in OS cells, while RNF180 knockdown showed the opposite effects. RNF180 also suppressed tumor growth and lung metastasis in mouse model, accompanied with elevated E-cadherin level and decreased ki-67 level. Besides, chromobox homolog 4 (CBX4) was predicted as a substrate of RNF180. RNF180 and CBX4 were both localized mainly in nucleus and their interaction was validated. RNF180 aggravated the decline of CBX4 level after cycloheximide treatment. RNF180 also promoted the ubiquitination of CBX4 in OS cells. Furthermore, CBX4 was significantly up-regulated in OS tissues. RNF180 also up-regulated Kruppel like factor 6 (KLF6) yet down-regulated RUNX family transcription factor 2 (Runx2) in OS, which served as downstream targets of CBX4. In addition, RNF180 inhibited migration, invasion and epithelial-mesenchymal transition (EMT) in OS cells, which were partially abolished by CBX4 over-expression. In conclusion, our findings demonstrated that RNF180 inhibits OS development via regulating CBX4 ubiquitination, and RNF180-CBX4 axis is a potential therapeutic target for OS treatment.

Hsa_circ_0014784-induced YAP1 promoted the progression of pancreatic cancer by sponging miR-214-3p

Abstract: ABSTRACT Background Pancreatic cancer (PC) is one of the most common gastrointestinal tumors globally. Former investigations discovered that circular RNAs (circRNAs) play an important role in PC development. circRNAs belong to a new class of endogenous noncoding RNAs, which have been found to mediate the progression of diverse types of tumors. Nevertheless, the roles of circRNAs and the underlying regulatory mechanisms in PC remain unknown. Methods In this study, our team employed next-generation sequencing (NGS) to examine the abnormal circRNA expression in PC tissues. The circRNA expression in PC cell lines and tissues was detected. Then, regulatory mechanism and targets were examined with bioinformatics analysis, luciferase reporting analysis, Transwell migration, 5-ethynyl−2′-deoxyuridine, and CCK−8 analysis. An in vivo experiment was employed to elucidate hsa_circ_0014784 roles in PC tumor growth and metastasis. Results The results showcased abnormal circRNA expression in PC tissues. Our lab also found that hsa_circ_0014784 expression incremented in PC tissues and cell lines, implying that hsa_circ_0014784 functioned in PC progression. hsa_circ_0014784 downregulation inhibited PC proliferation and invasion in vivo and in vitro. The bioinformatics and luciferase report data validated that both miR−214-3p and YAP1 were hsa_circ_0014784 binding partners. The overexpression of YAP1 reversed the migration, proliferation, and epithelial – mesenchymal transition (EMT) of PC cells and the angiogenic differentiation of HUVECs after miR−214-3p overexpression. Conclusion Taken together, our study found that hsa_circ_0014784 downregulation decremented invasion, proliferation, EMT, and angiogenesis of PC by regulating miR−214-3p/YAP1 signaling.

Systematic analysis of the oncogenic role of FAM83D across cancers based on data mining

Abstract: ABSTRACT Family with sequence similarity of 83D (FAM83D) is overexpressed in various cancers. However, no pan-cancer analysis is presently available. In the present study, we used a bioinformatics analysis to explore the diagnostic and prognostic value of FAM83D expression levels in human cancers. The GEPIA 2, TIMER 2.0, ENCORI, and DriverDBV3 databases were used to evaluate FAM83D expression levels. The potential prognostic value of FAM83D expression was analyzed using the GEPIA 2, UALCAN, and TISIB databases. The driver gene and promoter methylation levels regarding FAM83D were evaluated using the TIMER 2.0 and UALCAN databases. To further analyze interactive networks for FAM83D, FAM83D-binding proteins and related genes were determined using STRING and Gene MANIA analytic tools. Highly expressed FAM83D could be associated with mutated TP53 and promoter DNA methylation. Relative network analysis suggested that FAM83D was mainly involved in the progesterone-mediated oocyte maturation pathway, cell cycle regulation, and several other signaling pathways. Therefore, the differential expression of FAM83D could serve as a diagnostic and prognostic biomarker for various cancers. Our study revealed useful information about the differential expression of FAM83D, prognostic values, and potential functional networks in a variety of cancers, providing valuable substantive and methodological information to explore the underlying mechanisms. Abbreviations: BP: Biological processes; CC: Cellular components; DAVID: Database for Annotation, Visualization, and Integrated Discovery; DFS: Disease-free survival; ENCORI: Encyclopedia of RNA Interactomes; FAM83: Family with sequence similarity 83; FAM83D: Family with sequence similarity of 83D; GEO: Gene Expression Omnibus; GEPIAx2: Gene Expression Profiling Interactive Analysis 2; GO: Gene Ontology; GTEx: Genotype-Tissue Expression; KEGG: Kyoto Encyclopedia of Genes and Genomes; KIRC: Kidney renal clear cell carcinoma; LIHC: Liver hepatocellular carcinoma; LUAD: Lung adenocarcinoma; MF: Molecular functions miRNA: microRNA; OS: Overall survival; PAAD: Pancreatic adenocarcinoma; PPI: Protein – protein interaction; RNA-seq: RNA-sequencing; TCGA: The Cancer Genome Atlas; TIMER 2.0: Tumor Immune Estimation Resource 2.0; UALCAN: University of Alabama at Birmingham Cancer; UCEC: Uterine corpus endometrial carcinoma.

Statement of Retraction: Exosomes-carried microRNA-26b-5p regulates microglia M1 polarization after cerebral ischemia/reperfusion

Abstract: This article refers to:RETRACTED ARTICLE: Exosomes-carried microRNA-26b-5p regulates microglia M1 polarization after cerebral ischemia/reperfusion

Hsa_circ_0063329 inhibits prostate cancer growth and metastasis by modulating the miR-605-5p/tgif2 axis

Abstract: ABSTRACT Circular RNAs play crucial regulatory roles in the progression of various cancers. Nevertheless, the underlying mechanisms of circRNAs in prostate cancer (PCa) proliferation and metastasis remain largely uncertain. Here, we performed circRNA microarray analyses to identify differentially expressed circRNAs in a normal prostate epithelial cell line and PCa cell lines. We found that hsa_circ_0063329 was significantly downregulated in PCa. A series of in vitro and in vivo functional assays showed that overexpression of hsa_circ_0063329 inhibits PCa cell progression, while silencing of hsa_circ_0063329 achieved the opposite effects. Mechanistically, bioinformatics analysis, RNA pulldown, RNA-seq and dual-luciferase reporter assays demonstrated that hsa_circ_0063329 exerts its effect by sponging miR-605-5p to derepress TG-interacting factor 2 (TGIF2) and inactivate the TGF-β pathway. In conclusion, hsa_circ_0063329 inhibits the proliferation and metastasis of PCa via modulation of the miR-605-5p/TGIF2 axis, and targeting hsa_circ_0063329 may provide a promising treatment strategy for aggressive PCa.