Showing papers in "Cancer Biology & Therapy in 2019"
TL;DR: The major advancements of melanoma diagnosis and treatment from antiquity to the present day are discussed, with a focus on treatment for metastatic melanoma.
Abstract: Melanoma is the deadliest form of skin cancer. In the early stages, melanoma can be treated successfully with surgery alone and survival rates are high, but after metastasis survival rates drop sig...
336 citations
TL;DR: Tumor-specific, circulating cell-free DNA in liquid biopsies is a promising source of biomarkers for minimally invasive serial monitoring of treatment responses in cancer management and the role of circulating DNA in pathophysiological processes is reviewed.
Abstract: Tumor-specific, circulating cell-free DNA in liquid biopsies is a promising source of biomarkers for minimally invasive serial monitoring of treatment responses in cancer management. We will review the current understanding of the origin of circulating cell-free DNA and different forms of DNA release (including various types of cell death and active secretion processes) and clearance routes. The dynamics of extracellular DNA in blood during therapy and the role of circulating DNA in pathophysiological processes (tumor-associated inflammation, NETosis, and pre-metastatic niche development) provide insights into the mechanisms that contribute to tumor development and metastases formation. Better knowledge of circulating tumor-specific cell-free DNA could facilitate the development of new therapeutic and diagnostic options for cancer management.
268 citations
TL;DR: CIRS-7 can trigger the migration and invasion of ESCC cells via miR-7/KLF4 and NF-κB signals and targeted inhibition of ciRS- 7 might be a potential approach for ESCC treatment.
Abstract: Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent and deadly cancers worldwide, especially in Eastern Asia It has been indicated that circular RNAs (circRNA) are the key regulators in the development and progression of human cancers We therefore evaluated the expression and regulation effects of ciRS-7 on the progression of ESCC, which is a recently identified circRNA and acts as a natural competing endogenous RNA The expression of ciRS-7 was significantly increased in the ESCC tissues and cells as compared with their corresponding controls In vitro study showed that ciRS-7 can promote the migration and invasion of ESCC cells Over expression of miR-7, one of well-known targets of ciRS-7, can attenuate ciRS-7 induced invasion of ESCC cells and over expression of matrix metalloproteinase 2 (MMP2) The expression of stem cell marker Kruppel-like factor-4 (KLF-4), which has been reported as the target of miR7, increased significantly in ciRS-7 transfected ESCC cells Knockdown of KLF-4 also attenuated over expression of ciRS-7 induced cell invasion In addition, BAY 11-7082, the inhibitor of NF-κB, partially reversed ciRS-7 induced cell invasion Mechanically studies indicated that ciRS-7 increased the expression of p65 via increasing the phosphorylation of IKK-α Collectively, our present study revealed that ciRS-7 can trigger the migration and invasion of ESCC cells via miR-7/KLF4 and NF-κB signals Targeted inhibition of ciRS-7 might be a potential approach for ESCC treatment
102 citations
TL;DR: It is demonstrated that EGF secreted by M2-like TAMs might suppress LIMT expression via activating EGFR-ERK signaling pathway to promote the progression of OC.
Abstract: Background: Ovarian cancer (OC) is the gynecologic malignant tumor with high mortality. Accumulating evidence indicates that M2-like tumor-associated macrophages (TAMs) can secret EGF to participat...
80 citations
TL;DR: This review effectively compiles the role of CCSC surface markers and dysregulated and/or upregulated pathways in the pathogenesis of colorectal cancer that can be used to target CCSCs for effective coloreCTal cancer treatment.
Abstract: Despite incessant research, colon cancer still is one of the most common causes of fatalities in both men and women worldwide. Also, nearly 50% of patients with colorectal cancer show tumor recurrence. Recent investigations have highlighted the involvement of colon cancer stem cells (CCSCs) in cancer relapse and chemoresistance. CCSCs deliver a significant protumorigenic niche through persistent overexpression of self-renewal capabilities. Moreover, CSCs cross network with stromal cells, immune infiltrates, and cyotokine-chemokine, which potentiate their aggressive proliferative potential. Targeting CCSCs through small molecule inhibitors, miRNAs, and monoclonal antibodies (mAbs) in in vivo studies has generated compelling evidence for the effectiveness of these various treatments. This review effectively compiles the role of CCSC surface markers and dysregulated and/or upregulated pathways in the pathogenesis of colorectal cancer that can be used to target CCSCs for effective colorectal cancer treatment.
69 citations
TL;DR: The findings indicate that there is an miR-137/FSTL1/integrin β3/Wnt/β-catenin signaling axis in breast cancer cells that regulates stemness and chemoresistance.
Abstract: FSTL1 is a protein coding gene associated with cell signaling pathway regulation and the progression of a variety of disorders. In this study, we hypothesized that FSTL1 increases oncogenesis in breast cancer by enhancing stemness and chemoresistance. RT-PCR and IHC revealed significantly higher FSTL1 mRNA and protein levels in TNBC than in non-TNBC specimens and in breast cancer cell lines. We then found that FSTL1 levels were significantly increased in chemoresistant cells. LIVE/DEAD, MTT cell viability and colony formation assays did in fact demonstrate that FSTL1 is required for CDDP and DOX chemoresistance in breast cancer cell lines. FSTL1 overexpression caused significant elevation of stem cell biomarkers, as well as breast cancer cell proliferation. To determine whether the Wnt/β-catenin signaling pathway is involved in the observed effects of FSTL1, we assessed levels of pathway target. TOP/FOP flash, colony formation, and tumor sphere formation assays indicated that FSTL1 activates Wnt/β-catenin signaling through integrin β3. We then sought to identify a microRNA (miRNA) that regulates FSTL1 activity. Luciferase assays demonstrated that miR-137 reduces FSTL1 mRNA and protein levels. Ultimately, our findings indicate that there is an miR-137/FSTL1/integrin β3/Wnt/β-catenin signaling axis in breast cancer cells that regulates stemness and chemoresistance.
65 citations
TL;DR: Overexpression of SNHG5 and CREB5 resulted in the enhancement of proliferation, metastasis, migration and the inhibition of apoptosis in CRC cells, while miR-132-3p led to the opposite result.
Abstract: We aimed at the effects of long non-coding RNA (lncRNA) SNHG5 on proliferation, metastasis and migration of colorectal cancer (CRC) cells. We also investigated regulatory relationships among miR-132-3p, SNHG5 and CREB5 and their roles in CRC. 25 pairs of samples containing CRC tissues and matched para-tumor tissues were obtained to examine SNHG5, miR-132-3p and CREB5 expression by qRT-PCR or Western blot. The targeted relationship between miR-132-3p and SNHG5 or CREB5 was confirmed by dual luciferase report assay as well as RNA pull down assay. The expression of SNHG5, miR-132-3p and CREB5 in CRC cells were regulated by cell transfection. CRC cellular proliferation was assayed by CCK-8 and meanwhile flow cytometry was adopted to observe apoptosis. Metastasis and migration of CRC cells were determined respectively by means of Transwell assay and scratch test. The effects of SNHG5 on CRC were researched in vivo, too. SNHG5 or CREB5 was up-regulated in CRC tissues and cells, whereas miR-132-3p was down-regulated. Overexpression of SNHG5 and CREB5 resulted in the enhancement of proliferation, metastasis, migration and the inhibition of apoptosis in CRC cells, while miR-132-3p led to the opposite result. LncRNA SNHG5 promoted proliferation, migration and metastasis of CRC cells but inhibited apoptosis by modulating miR-132-3p/CERB5.
63 citations
TL;DR: It is revealed that ZEB1-induced upregulation of KCNQ1OT1 improved the proliferation, migration and EMT formation of CRC cells via regulation of miR-217/ZEB1 axis.
Abstract: Long noncoding RNAs are widely acknowledged as a group of regulatory factors in various diseases, especially in cancers. KCNQ1 overlapping transcript 1 (KCNQ1OT1) has been reported as oncogene in human cancers. However, the role of KCNQ1OT1 in colorectal cancer (CRC) has not been fully explained. Based on the database analysis, KCNQ1OT1 was highly expressed in CRC samples and predicted the poor prognosis for CRC patients. Functional experiments revealed that KCNQ1OT1 knockdown negatively affected the proliferation, migration and epithelial-mesenchymal transition (EMT) in CRC cells. Moreover, we identified the cytoplasmic localization of KCNQ1OT1 in CRC cells, indicating the post-transcriptional regulation of KCNQ1OT1 on gene expression. Mechanism experiments including RNA Immunoprecipitation (RIP) assay and dual luciferase reporter assays verified that KCNQ1OT1 acted as a competing endogenous RNA (ceRNA) in CRC by sponging microRNA-217 (miR-217) to up-regulate the expression of zinc finger E-box binding homeobox 1 (ZEB1). Further mechanism investigation revealed that ZEB1 enhanced the transcription activity of KCNQ1OT1 by acting as a transcription activator. Finally, rescue assays were designed to demonstrate the effect of KCNQ1OT1-miR-217-ZEB1 feedback loop on proliferation, migration, and EMT of CRC cells. In brief, our research findings revealed that ZEB1-induced upregulation of KCNQ1OT1 improved the proliferation, migration and EMT formation of CRC cells via regulation of miR-217/ZEB1 axis.
52 citations
TL;DR: It was uncovered that the expression of Notch1 and Hes1 (the core factors of NotCh signaling pathway) was negatively regulated by HNF1A-AS1 knockdown, which promotes OSCC progression by activating Notch signaling pathway.
Abstract: Long non-coding RNAs (lncRNAs) are a group of biomarkers which can regulate the biological processes of various human cancers. LncRNA HNF1A-AS1 has been reported in human cancers for its oncogenic role. This study focused on the biological function and molecular mechanism of HNF1A-AS1 in oral squamous cell carcinoma (OSCC). The high expression of HNF1A-AS1 was examined in OSCC tissues and cell lines. Kaplan Meier method revealed that high expression of HNF1A-AS1 predicted poor prognosis for patients with OSCC. Results of loss-of-function assays demonstrated that silenced HNF1A-AS1 inhibited the proliferation, migration and epithelial-mesenchymal transition (EMT) of OSCC cells. Mechanically, HNF1A-AS1 was positively regulated by the transcription factor STAT3. Recently, Notch signaling pathway has been reported in human malignancies. In this study, we analyzed the correlation between HNF1A-AS1 and Notch signaling pathway. It was uncovered that the expression of Notch1 and Hes1 (the core factors of Notch signaling pathway) was negatively regulated by HNF1A-AS1 knockdown. Rescue assays further demonstrated the positive regulatory effects of HNF1A-AS1 on Notch signaling pathway in OSCC. In conclusion, upregulation of HNF1A-SA1 induced by transcription factor STAT3 promotes OSCC progression by activating Notch signaling pathway.
50 citations
TL;DR: The regulatory role of GSK-3β in apoptosis, cell cycle, DNA repair, tumor growth, invasion, and metastasis reflects the therapeutic relevance of this target and provides the rationale for drug combinations.
Abstract: As a kinase at the crossroads of numerous metabolic and cell growth signaling pathways, glycogen synthase kinase-3 beta (GSK-3β) is a highly desirable therapeutic target in cancer. Despite its involvement in pathways associated with the pathogenesis of several malignancies, no selective GSK-3β inhibitor has been approved for the treatment of cancer. The regulatory role of GSK-3β in apoptosis, cell cycle, DNA repair, tumor growth, invasion, and metastasis reflects the therapeutic relevance of this target and provides the rationale for drug combinations. Emerging data on GSK-3β as a mediator of anticancer immune response also highlight the potential clinical applications of novel selective GSK-3β inhibitors that are entering clinical studies. This manuscript reviews the preclinical and early clinical results with GSK-3β inhibitors and delineates the developmental therapeutics landscape for this potentially important target in cancer therapy.
50 citations
TL;DR: The following are reviewed: temozolomide discovery, chemistry, and mechanism of action, and mechanisms of resistance, as well as combination therapy with other strategies.
Abstract: Glioblastoma is the most invasive form of brain tumor. Although temozolomide chemotherapy has been shown to significantly improve survival in patients with GBM, this increase is only trivial. The underlying cause is that many GBMs do not respond to temozolomide, and the rest produces resistance. In the past two decades, many attempts have been made to understand resistance mechanisms and to combine other treatments with temozolomide to maximize patient benefit. Unfortunately, it seems to be a red queen game, and the speed of disease development is as fast as the progress in the field. In order to win this game, a comprehensive approach is needed to decipher the details of the resistance mechanism and to transfer the basic research to the clinic. This article reviews the following: temozolomide discovery, chemistry, and mechanism of action, and mechanisms of resistance, as well as combination therapy with other strategies.
TL;DR: The data suggest that circ-MTO1 is a critical negative regulator of LUAD and elucidate the potential molecular mechanism of a novel circ- MTO1/miR-17/QKI-5 feedback loop in inhibiting LUAD progression.
Abstract: Circular RNA (circRNA) is a new class of non-coding RNA that plays a pivotal role in carcinogenesis. Recently, circ-MTO1 (hsa_circ_0007874) was shown to be a cancer-related circRNA. However, its role in lung adenocarcinoma (LUAD) has not been reported. Here, we found that circ-MTO1 was significantly down-regulated in LUAD, which was closely associated with malignant features and dismal prognosis. Enforced expression of circ-MTO1 suppressed the growth of LUAD cells both in vitro and in vivo. Subsequent mechanism experiments showed that circ-MTO1 served as a sponge of oncogenic miR-17 to increase the expression of RNA-binding protein QKI-5, leading to the inactivation of Notch signaling pathway, thereby restraining the growth of LUAD. Importantly, increased QKI-5 expression caused by circ-MTO1 overexpression in turn promoted circ-MTO1 expression. Clinically, circ-MTO1 expression was strongly positively correlated with QKI-5 expression, but negatively correlated with miR-17 expression. Taken together, our data suggest that circ-MTO1 is a critical negative regulator of LUAD and elucidate the potential molecular mechanism of a novel circ-MTO1/miR-17/QKI-5 feedback loop in inhibiting LUAD progression.
TL;DR: It is concluded that LEF1-AS1 served an oncogenic part in OSCC through suppressing Hippo signaling pathway by interacting with LATS1, suggesting the therapeutic and prognostic potential of LEF/AS1 in OS CC.
Abstract: It is verified that long non-coding RNAs (lncRNAs) play crucial roles in various cancers. LncRNA LEF1-AS1 is a reported oncogene in colorectal cancer and glioblastoma. In this study, we unveiled that LEF1-AS1 markedly increased in oral squamous cell carcinoma (OSCC) tissues and cell lines. Besides, OSCC patients with high levels of LEF1-AS1 were apt to poor prognosis. Functionally, LEF1-AS1 knockdown inhibited cell survival, proliferation and migration, whereas enhanced cell apoptosis and induced G0/G1 cell cycle arrest in vitro. Consistently, LEF1-AS1 silence hindered tumor growth in vivo. Moreover, LEF1-AS1 inhibition stimulated the activation of Hippo signaling pathway through directly interacting with LATS1. Furtherly, we disclosed that LEF1-AS1 silence abolished the interaction of LEF1-AS1 with LATS1 while enhanced the binding of LATS1 to MOB, therefore promoting YAP phosphorylation but impairing YAP1 nuclear translocation. Additionally, we demonstrated that LEF1-AS1 regulated YAP1 translocation via a LATS1-dependent manner. Furthermore, we also uncovered that YAP1 overexpression abolished the suppressive impact of LEF1-AS1 repression on the biological processes of OSCC cells. In a word, we concluded that LEF1-AS1 served an oncogenic part in OSCC through suppressing Hippo signaling pathway by interacting with LATS1, suggesting the therapeutic and prognostic potential of LEF1-AS1 in OSCC.
TL;DR: It is demonstrated that MSC-AS1/miR-29b-3p axis modulates the cell proliferation and GEM-induced cell apoptosis in PDAC cell lines through CDK14.
Abstract: Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related death due to the failure of traditional therapies. In the present study, we attempted to construct a lncRNA-miRNA-mRNA network which may modulate PDAC cell proliferation and Gemcitabine-induced cell apoptosis starting from CDK14, a new member of the CDK family and an oncogene in many cancers. Based on TCGA data, a significant positive correlation was observed between lncRNA MSC-AS1 and CDK14. Moreover, MSC-AS1 expression was upregulated in PDAC tissues. Higher MSC-AS1 expression was correlated with poorer prognosis in patients with PDAC. MSC-AS1 knockdown in Panc-1 and BxPC-3 cells significantly inhibited the cell proliferation. Moreover, miR-29b-3p, which has been reported to act as a tumor suppressor, was predicted to bind to both MSC-AS1 and CDK14. Contrary to MSC-AS1, higher miR-29b-3p expression was correlated to better prognosis in patients with PDAC. In both PDAC cell lines, miR-29b-3p negatively regulated MSC-AS1 and CDK14. As confirmed using luciferase reporter gene and RIP assays, MSC-AS1 served as a ceRNA for miR-29b-3p to counteract miR-29b-mediated CDK14 repression. MSC-AS1 knockdown inhibited CDK14 protein levels and PDAC proliferation and enhanced gemcitabine-induced cell death and apoptosis while miR-29b-3p inhibition exerted an opposing effect; the effect of MSC-AS1 knockdown was partially attenuated by miR-29b-3p inhibition. Taken together, we demonstrated that MSC-AS1/miR-29b-3p axis modulates the cell proliferation and GEM-induced cell apoptosis in PDAC cell lines through CDK14. We provided a novel experimental basis for PDAC treatment from the perspective of lncRNA-miRNA-mRNA network.
TL;DR: It is found that MS-444 treatment of glioblastoma cells resulted in loss of viability and induction of apoptosis, with evidence implicating death receptor 5.0, and this report provides proof of concept that small molecule inhibition of HuR could be a viable approach for treatment of adenocarcinoma.
Abstract: Glioblastoma is a highly malignant and typically fatal tumor of the central nervous system. The tumor is characterized by marked cellular and molecular heterogeneity, including a subpopulation of brain tumor initiating cells (BTICs) that are highly resistant to radiation and chemotherapy. We previously reported that the RNA-binding protein HuR is: (1) overexpressed in glioblastoma, (2) necessary for tumor growth in vivo, and (3) a positive regulator of tumor-promoting genes in glioblastoma. These findings provide strong evidence that HuR might be a viable therapeutic target in glioblastoma. In this report, we investigated the effects of MS-444, a small molecule inhibitor of HuR, in xenograft-derived human glioblastoma cells and BTICs. We found that MS-444 treatment of glioblastoma cells resulted in loss of viability and induction of apoptosis, with evidence implicating death receptor 5. BTICs were particularly sensitive to MS-444. At sub-lethal doses, MS-444 attenuated invasion of glioblastoma cells and BTICs in a transwell model. At the molecular level, MS-444 treatment led to an attenuation of mRNAs in different tumor promoting pathways including angiogenesis, immune evasion and suppression of apoptosis. Although cytoplasmic HuR was reduced with MS-444 treatment, the attenuation of mRNAs could not be explained by RNA destabilization. In summary, this report provides proof of concept that small molecule inhibition of HuR could be a viable approach for treatment of glioblastoma.
TL;DR: Lamc1 was implicated in the progression of HCC probably by regulating PKM2 expression through PTEN/AKT pathway, and it was speculated that Lamc1-induced increase in PKM 2 expression was strongly attenuated by a PI3K inhibitor.
Abstract: Hepatocellular carcinoma (HCC), the most common aggressive malignancy of liver, is the third leading cause of cancer death across the world. Laminin gamma 1 (Lamc1), encodes laminin-γ1, an extracellular matrix protein involved in various progresses such as tumor cell proliferation and metabolism. In the present study, high expression of Lamc1 and PKM2 was observed in tumor tissues of HCC patients. In vitro, down-regulation of Lamc1 inhibited proliferation of HCC cells by promoting cell death, reduced glucose consumption and lactate production, accompanied by a decrease in the expression of glucose transporter 1 (GLUT1) and lactate dehydrogenase A (LDHA), and PTEN increased, as well as PTEN S380 and AKT S473/T308 phosphorylation decreased, while Lamc1 up-regulation had the opposite effect. The effects of PKM2 were similar to that of Lamc1 and markedly counteracted the effects of Lamc1 down-regulation. In addition, Lamc1-induced increase in PKM2 expression was strongly attenuated by a PI3K inhibitor, LY294002 or a si-p110 PI3K, with a significant decrease in GLUT1 and LDHA expression, as well as decreased AKT T308 phosphorylation. Thus, we speculated that Lamc1 was implicated in the progression of HCC probably by regulating PKM2 expression through PTEN/AKT pathway.
TL;DR: The result of quantitative reverse transcription-polymerase chain reaction (qRT-PCR) reveals that miR-202-5p was highly expressed in drug-resistant breast cancer tissues, while PTEN was expressed less, and it was found that the overexpression of miR+5p promoted the DOX resistance and proliferation as well as decreased apoptosis of MCF-7 cells.
Abstract: We intended to explore the effect of miR-202-5p and phosphatase and tensin homolog (PTEN) on doxorubicin (DOX) resistance of breast cancer cells. The result of quantitative reverse transcription-polymerase chain reaction (qRT-PCR) reveals that miR-202-5p was highly expressed in drug-resistant breast cancer tissues, while PTEN was expressed less. MiR-202-5p directly targeted PTEN. Further, it was found that the overexpression of miR-202-5p promoted the DOX resistance and proliferation as well as decreased apoptosis of MCF-7 cells. The lower expression of miR-202-5p inhibited DOX resistance and proliferation as well as increased the apoptosis of MCF-7/DOX cells. In vivo experiments showed that mice with downregulated miR-202-5p had smaller tumor volume and lower Ki67 level. The overexpression of PTEN declined the proliferation of MCF7 cells, while miR-202-5p's overexpression could offset the function of overexpression of PTEN. The knockdown of PTEN promoted MCF7/DOX cell proliferation that could be counteracted by miR-202-5p silence. Moreover, we also revealed that downregulated miR-202-5p expression inhibited PI3k/Akt signaling pathway-related protein by regulating expression of PTEN.
TL;DR: TATDN1 enhanced the DDP-tolerance of NSCLC cells by upregulating TRIM66 expression via sponging miR-451, hinting a novel regulatory pathway of chemoresistance in D DP-tolerant NSclC cells and providing a potential therapeutic target for NSCLc patients with DDP -reistance.
Abstract: Background: Chemoresistance has been considered to be a major obstacle for cancer therapy clinically. Long non-coding RNAs (LncRNAs) are asscociated with the development, prognosis and drug-resista...
TL;DR: The findings implied that LINC00963/miR-204-3p/FN1 can play an important role in proliferation and progression in osteosarcoma.
Abstract: Purpose: It remains unclear that long noncoding RNAs' role in cancer initiation and progression, including osteosarcoma. Long noncoding RNA LINC00963 was found to be participated in carcinogenesis and progression of osteosarcoma. However, the molecular mechanisms of LINC00963 engaged in osteosarcoma (OS) still needs to be explored. Methods: LINC00963 and miR-204-3p RNA expression levels were quantified by PCR in OS tissues and cells. CCK 8 assay, wound healing assay and transwell migration and invasion assay were chosen to assess cell growth, viability, migration, and invasion. Luciferase reporter assays were performed to verify direct interaction between LINC00963 and miR-204-3p and miR-204-3p and Fibronectin-1. Western blot was conducted to evaluate Fibronectin-1 expression in OS cells. Results: LINC00963 was verified to be highly expressed in OS samples and cells. Specifically, elevated expression of LINC00963 was correlated with poor prognosis in patients. Furthermore, LINC00963 overexpression was found to promote proliferation, migration, and invasion in vitro. The luciferase reporter assay showed that LINC00963 can suppress miR-204-3p by directly binding miR-204-3p. Rescue experiment results indicated that function of LINC00963 in osteosarcoma was miR-204-3p dependant. Besides, we initially explored Fibronectin-1 (FN1) as the target of LINC00963/miR-204-3p axis in osteosarcoma. Conclusions: Our findings implied that LINC00963/miR-204-3p/FN1 can play an important role in proliferation and progression in osteosarcoma. LINC00963 has the potential to be a therapeutic target for osteosarcoma treatment.
TL;DR: In this paper, the role of long non-coding RNAs (lncRNAs) is discovered to be significant for the canceration and cancer progression, and the objective of the study is to unfold function and mechanism investigation on LINC00958 in OSCC.
Abstract: Oral squamous cell carcinoma (OSCC), the subtype of head and neck cancers, is notorious for its high incidence and death rate. The role of long non-coding RNAs (lncRNAs) is discovered to be significant for the canceration and cancer progression. Long intergenic non-protein coding RNA 958 (LINC00958) is discovered as a carcinogene in multiple cancers, such as gastric cancer, pancreatic cancer, and glioma, but there has been no report about how LINC00958 functions in OSCC. The objective of our study is to unfold function and mechanism investigation on LINC00958 in OSCC. First, TCGA database showed the upregulation and prognostic significance of LINC00958 in head and neck squamous carcinoma. Then, we discovered in OSCC clinical samples that LINC00958 presented high expression and predicted poor prognosis. Also, LINC00958 was elevated in OSCC cells. In vitro gain- and loss-function experiments proved that LINC00958 facilitated cell growth, retarded apoptosis, accelerated migration, and epithelial-to-mesenchymal transition (EMT) in OSCC. Mechanistically, we confirmed the cytoplasmic expression of LINC00958 in OSCC cells, and revealed that LINC00958 sequestered miR-627-5p to upregulate YBX2 expression. Rescue assays indicated that LINC00958 regulated OSCC cell proliferation, motility and EMT through YBX2. Together, we showed that LINC00958 promoted OSCC progression through miR-627-5p/YBX2 axis, indicating LINC00958 as a new prognostic marker, and provided new perspectives for molecular targeted treatment for OSCC.
TL;DR: A novel NIR-PIT technique to target CAFs, by focusing on fibroblast activation protein (FAP), was safe and showed a promising inhibitory effect on FAP+ CAFs.
Abstract: Cancer-associated fibroblasts (CAFs) are strongly implicated in tumor progression, including in the processes of tumorigenesis, invasion, and metastasis. The targeting of CAFs using various therape...
TL;DR: The properties, biogenesis, biological function, and research progress of circRNAs in lung cancer are discussed to provide a theoretical foundation and new directions for studies on circRN as new targets for tumor prediction and treatment.
Abstract: Lung cancer is one of the most common cancers and the leading cause of cancer-related death worldwide. Despite encouraging results achieved with targeted therapy in recent years, the early diagnosis and treatment of lung cancer remains a major problem. Circular RNA (circRNA), a type of RNA with covalently closed continuous loop structures, has structural stability and certain tissue specificity. Recent studies have found that circRNAs have an important role in tumor development and are expected to be revealed as new targets for tumor prediction and treatment. Research on the biological functions and regulation mechanisms of circRNAs in lung cancer is in its infancy but is gathering momentum. In this review, we discuss the properties, biogenesis, biological function, and research progress of circRNAs in lung cancer to provide a theoretical foundation and new directions for studies on circRNAs in lung cancer.
TL;DR: In this paper, the authors evaluated apatinib's efficacy and safety in advanced hepatocellular carcinoma (HCC) patients with TACE and showed that the combination therapy had a dramatic effect on OS and PFS.
Abstract: As a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor (VEGFR2-TKI), apatinib has a certain anti-tumor effect for a variety of solid tumors. The present study evaluates its efficacy and safety in advanced hepatocellular carcinoma (HCC). In this study, 47 patients with advanced HCC were included. TACE monotherapy group included 22 patients that responded to TACE, while the group that received TACE and apatinib included 25 patients that progressed on TACE and were able to receive apatinib off label. Median overall survival (OS) was significantly improved in the apatinib plus TACE group compared with the TACE group. Similarly, apatinib in combination with TACE significantly prolonged median progression-free survival (PFS) compared with TACE monotherapy. Furthermore, there was a significant difference between combination therapy and monotherapy in both Barcelona clinic liver cancer (BCLC) B and BCLC C group. The combination therapy had a dramatic effect on OS and PFS for patients at both BCLC B and BCLC C level. The most common clinically adverse events of apatinib plus TACE group were fatigue, weight loss, hypertension, hand-foot syndrome and anorexia, which were manageable and tolerable. The efficacy analysis showed that there was no significant association of survival benefit with age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, hypertension and hand-foot syndrome. Patients with macrovascular invasion and extrahepatic invasion showed worse survival benefits. In conclusion, apatinib combined with TACE revealed certain survival benefits for HCC patients who experienced progression following TACE, which can provide a promising strategy for HCC treatment.
TL;DR: Many CRC patients have abnormal lipid metabolism, and the intestinal microbiota is altered in these CRC patients, which may be involved in lipid metabolism abnormality in CRC patients.
Abstract: Background: Abnormal lipid metabolism is considered to be one of main promoters of colorectal cancer (CRC), and intestinal microorganisms may be involved in CRC in patients with abnormal lipid meta...
TL;DR: Systematic understanding of the role of exosomal lncRNAs in carcinogenesis may offer ideal diagnostic and prognostic biomarker or even therapeutic targets for malignancies.
Abstract: Cancer is one of the most pervasive causes of morbidity and mortality worldwide regardless of the fact that a majority of therapeutic strategies have been constantly invented. The survival rate of ...
TL;DR: The data demonstrate that neratinib + entinostat down-regulates oncogenic RAS and the two keyOncogenic drivers present in most uveal melanoma patients and causes a multifactorial form of killing via mitochondrial dysfunction and toxic autophagy.
Abstract: There is no efficacious standard of care therapy for uveal melanoma. Unlike cutaneous disease, uveal melanoma does not exhibit RAS mutations but instead contains mutations with ~90% penetrance in either Gαq or Gα11. Previously we demonstrated that neratinib caused ERBB1/2/4 and RAS internalization into autolysosomes which resulted in their proteolytic degradation. In PDX isolates of uveal melanoma, neratinib caused the internalization and degradation of Gαq and Gα11 in parallel with ERBB1 breakdown. These effects were enhanced by the HDAC inhibitor entinostat. Similar data were obtained using GFP/RFP tagged forms of K-RAS V12. Down regulation of Gαq and Gα11 expression and RAS-GFP/RFP fluorescence required Beclin1 and ATG5. The [neratinib + entinostat] combination engaged multiple pathways to mediate killing. One was from ROS-dependent activation of ATM via AMPK-ULK1-ATG13-Beclin1/ATG5. Another pathway was from CD95 via caspase 8-RIP1/RIP3. A third was from reduced expression of HSP70, HSP90, HDAC6 and phosphorylation of eIF2α. Downstream of the mitochondrion both caspase 9 and AIF played roles in tumor cell execution. Knock down of ATM/AMPK/ULK-1 prevented ATG13 phosphorylation and degradation of RAS and Gα proteins. Over-expression of activated mTOR prevented ATG13 phosphorylation and suppressed killing. Knock down of eIF2α maintained BCL-XL and MCL-1 expression. Within 6h, [neratinib + entinostat] reduced the expression of the immunology biomarkers PD-L1, ODC, IDO-1 and enhanced MHCA levels. Our data demonstrate that [neratinib + entinostat] down-regulates oncogenic RAS and the two key oncogenic drivers present in most uveal melanoma patients and causes a multifactorial form of killing via mitochondrial dysfunction and toxic autophagy. Abbreviations: ERK: extracellular regulated kinase; PI3K: phosphatidyl inositol 3 kinase; ca: constitutively active; dn: dominant negative; ER: endoplasmic reticulum; AIF: apoptosis inducing factor; AMPK: AMP-dependent protein kinase; mTOR: mammalian target of rapamycin; JAK: Janus Kinase; STAT: Signal Transducers and Activators of Transcription; MAPK: mitogen activated protein kinase; PTEN: phosphatase and tensin homologue on chromosome ten; ROS: reactive oxygen species; CMV: empty vector plasmid or virus; si: small interfering; SCR: scrambled; IP: immunoprecipitation; VEH: vehicle; HDAC: histone deacetylase.
TL;DR: CSF provides a more comprehensive profile of LM than plasma in a large cohort, thus can be used as an alternative source of liquid biopsy for LM patients.
Abstract: Background: Leptomeningeal metastases (LM), associated with poor prognosis, are frequent complications of advanced non-small cell lung cancer (NSCLC) patients, especially in patients with epidermal...
TL;DR: It is demonstrated that miR-21 promotes the tumorigenesis of PCa cells by directly targeting KLf5 and inhibited KLF5 mRNA and protein levels in PCa.
Abstract: Prostate cancer (PCa) is the second frequently newly diagnosed cancer in men. Androgen deprivation therapy has been widely used to inhibit PCa growth but eventually fails in many patients. Androgen receptor and its downstream molecules like microRNAs could be promising therapeutic targets. We aimed to investigate the involvement of miR-21 in PCa tumorigenesis. We found that miR-21 was an unfavorable factor and correlated positively with tumor grade in PCa patients from TCGA database. MiR-21 was more highly expressed in androgen-independent PCa cells than in androgen-dependent PCa cells. Overexpression of miR-21 promoted androgen-dependent and -independent PCa cell proliferation, migration, invasion, and resistance to apoptosis. Furthermore, increased miR-21 expression promoted mouse xenograft growth. We identified nine genes differentially expressed in PCa tumors and normal tissue which could be potential targets of miR-21 by bioinformatic analyses. We demonstrate that miR-21 directly targeted KLF...
TL;DR: Targeting miR-155 in NKTCL cells significantly boosted BRG1 expression and decreased the activated STAT3 or VEGFC level, leading to enhanced apoptosis and reduced lymphangiogenesis, and providing a novel therapy forNKTCL.
Abstract: Background: miR-155 was up-regulated in natural killer/T-cell lymphoma (NKTCL), an aggressive malignancy, and correlated with disease progression. However, minimal is known on biological activities...
TL;DR: It is demonstrated that EGR1-induced upregulation of lncRNA FOXD2-AS1 promotes the progression of hepatocellular carcinoma via epigenetically silencing DKK1 and activating Wnt/β-catenin signaling pathway.
Abstract: Long non-coding RNAs (lncRNAs) are regarded as a group of biomarkers in the initiation and development of various cancers, including hepatocellular carcinoma (HCC). LncRNA FOXD2-AS1 has been studie...