ABSTRACT Chemoresistance in hepatocellular carcinoma (HCC) has been found to be influenced by exosomal transport of circRNAs. However, the role of circZFR in HCC chemoresistance still remains unclear. In the present study, circZFR was highly expressed in cisplatin (DDP)-resistant HCC cell lines and could regulate DDP resistance of the HCC cells. Also, circZFR was highly expressed in cancer-associated fibroblast (CAFs) and the exosome of CAFs. In addition, supplementation of CAFs in culture medium could promote DDP resistance of HCC cells. In vivo tumor xenograft experiments showed that knockdown of circZFR inhibited tumor growth and weakened DDP resistance, while CAFs-derived exosomes incubation increased the expression of circZFR, inhibited the STAT3/NF-κB pathway, promoted tumor growth, and enhanced DDP resistance. In general, CAFs-derived exosomes deliver circZFR to HCC cells, inhibit the STAT3/NF-κB pathway, and promote HCC development and chemoresistance. The results provided a new sight for the prevention and treatment of chemoresistance in HCC. Graphical abstract

https://www.tandfonline.com/doi/pdf/10.1080/21655979.2022.2032972?needAccess=true

Cancer-associated fibroblast exosomes promote chemoresistance to cisplatin in hepatocellular carcinoma through circZFR targeting signal transducers and activators of transcription (STAT3)/ nuclear factor -kappa B (NF-κB) pathway

Circular RNAs (circRNAs) are a type of endogenous non-coding RNAs implicated in cancer progression. This study explored the expression levels, clinical implication and possible molecular mechanism of circRNA_102231 in gastric cancer (GC). Gene Expression Omnibus (GEO) was used to analyze differentially expressed circRNAs. CircRNA_102231 expression was verified by qRT-PCR in GC tissues and plasma. The effects of circRNA_102231 was tested by CCK-8, colony formation, EdU and Transwell assays and xenograft tumor model. RNA pull-down and immunoprecipitation (RIP) assays were used to analyze the interaction between circRNA_102231 and IRTKS. CircRNA_102231 expression was significantly upregulated in GC tissue and plasma samples, which can be used as a biomarker for GC diagnosis and prognosis. The function assays showed that circRNA_102231 knockdown inhibited GC cell proliferation and invasion both in vitro and in vivo. CircRNA_102231 was able to bind to IRTKS, increasing IRTKS protein stability, leading to GC progression. Overexpression of IRTKS effectively rescued the reduced cell viability and invasion caused by silencing of circRNA_102231. In sum, our data demonstrate that circRNA_102231 is a novel oncogene in GC and acts as a potential biomarker and therapeutic target for GC patients.AbbreviationscircRNAs: circular RNAs; GC: gastric cancer; GEO: Gene Expression Omnibus; RIP: RNA immunoprecipitation; DEGs: differentially expressed genes.

Upregulated circRNA_102231 promotes gastric cancer progression and its clinical significance.

MiR-1298-5p level downregulation induced by Helicobacter pylori infection inhibits autophagy and promotes gastric cancer development by targeting MAP2K6.

With the gradual recognition of the side effects of local anesthetics, the nerve injury caused by local anesthetics has received growing attention. This research intended to delve into miR-183-5p changes in mepivacaine-mediated SH-SY5Y cell injury, as well as its modulatory mechanism on cell apoptosis. RT-qPCR was adopted for assaying miR-183-5p and PDCD4 mRNA expression. Our team respectively transfected miR-183-5p mimic and inhibitor to enhance or inhibit miR-183-5p function. We employed Western blot for detecting PDCD4 protein levels, as well as flow cytometry and Hoechst 33342/PI double staining for determining cell apoptosis rate. Additionally, our crew applied an ELISA kit for measuring TNF-α, IL-1β, IL-6, and IL-8 contents. The level of reactive oxygen species (ROS) production was examined by the Image-iT LIVE Green ROS detection Kit. As well as dual-luciferase reporter experiment for verifying the targeting link of miR-183-5p with PDCD4. In mepivacaine-induced cell apoptosis in SH-SY5Y cells, miR-183-5p expression was down-regulated. TNF-α, IL-1β, IL-6, and IL-8 contents were elevated. The rate of apoptosis increased visibly, cleaved caspase-3 and Bax levels waxed, whereas Bcl-2 level waned. MiR-183-5p could alleviate the damaging impact of mepivacaine. Dual-luciferase reporter experiments demonstrated that miR-183-5p directly targeted PDCD4. Collectively, we concluded that a high concentration of mepivacaine can cause SH-SY5Y cell damage, miR-183-5p functions crucially in mepivacaine-mediated cell damage. This study provides a theoretical basis for elucidating the mechanism of mepivacaine-induced nerve cell damage, and overexpressed miR-183-5p likely become a novel strategy to combat mepivacaine-induced nerve damage.Abbreviations:miRNA: Micro RNA; PDCD4: Programmed Cell Death 4; MDA: Malondialdehyde; SOD: Superoxide Dismutase; ROS: Reactive Oxygen Species; WT: Wild Type; Mut: Mutant; UTR: Untranslated Region; IL-6: Interleukin-6; IL-1β: Interleukin-1β; TNF-α: Tumor Necrosis Factor-α; IL-8: Interleukin-8; COX-2: Cyclooxygenase-2; iNOS: inducible NOS; MEP: Mepivacaine.

https://www.tandfonline.com/doi/pdf/10.1080/21655979.2021.1946358

MicroRNA-183-5p protects human derived cell line SH-SY5Y cells from mepivacaine-induced injury.

Circular RNAs (circRNAs), a group of unique long noncoding RNAs, are involved in gastric carcinogenesis through multiple mechanisms, including interacting with microRNAs (miRNAs). Here, circ0005654, significantly upregulated in gastric cancer (GC), was chosen for further examination. circ0005654 was analyzed by RT-qPCR. The function of circ0005654 in GC cells was substantiated by loss-of-function assays. The mechanism of circ0005654 on miR-363/specificity protein 1 (sp1) axis was evaluated in GC cells by bioinformatics analysis, luciferase reporter, FISH, and ChIP assays. We observed that circ0005654 was enhanced in GC tissues and cells. Overexpression of circ0005654 was correlated with a poor long-term prognosis in patients with GC. Functionally, silencing of circ0005654 remarkably suppressed GC cell proliferation, migration and invasiveness in vitro and tumorigenesis and metastases in vivo. It was also established that circ0005654 served as a miR-363 sponge and enhanced sp1 expression. Furthermore, sp1 promoted GC carcinogenesis by regulating myc transcription to potentiate the Wnt/β-catenin pathway. In conclusion, circ0005654 expedites the GC development via miR-363/sp1/myc/Wnt/β-catenin axis and is a new biomarker for GC treatment regimen.

The circular RNA circ0005654 interacts with specificity protein 1 via microRNA-363 sequestration to promote gastric cancer progression.

Non-small cell lung cancer (NSCLC) is a common malignant tumor, with high morbidity and mortality. Circular RNA (circRNA) circ_0003028 was reported to be upregulated in NSCLC. This study is designed to explore the role and mechanism of circ_0003028 on NSCLC progression. In this work, circ_0003028, microRNA-1298-5p (miR-1298-5p), and glutamic oxaloacetic transaminase 2 (GOT2) level were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The localization of circ_0003028 was analyzed by subcellular fractionation assay. Cell proliferation, colony number, cell cycle progression, apoptosis, migration, invasion, and angiogenesis were measured by Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, transwell, and tube formation assays. Protein levels of Beclin1, light chain 3 (LC3)-II/LC3-I, GOT2, proliferating cell nuclear antigen (PCNA) were examined by western blot assay. The binding relationship between miR-1298-5p and circ_0003028 or GOT2 was predicted by circular RNA Interactome or starbase and then verified by dual-luciferase reporter, RNA Immunoprecipitation (RIP), and RNA pull-down assays. The biological role of circ_0003028 on NSCLC tumor growth was examined by the xenograft tumor model in vivo. We reported that circ_0003028 and GOT2 were upregulated, and miR-1298-5p was decreased in NSCLC tissues and cells. Moreover, circ_0003028 knockdown curbed cell proliferative ability, migration, invasion, angiogenesis, and facilitate apoptosis and autophagy in NSCLC cells in vitro. Mechanical analysis discovered that circ_0003028 regulated GOT2 expression by sponging miR-1298-5p. Circ_0003028 silencing hindered the cell growth of NSCLC in vivo. Taken together, circ_0003028 knockdown could suppress NSCLC progression partly by regulating the miR-1298-5p/GOT2 axis, providing an underlying therapeutic target for NSCLC.

https://www.tandfonline.com/doi/pdf/10.1080/21655979.2021.1935064

Jinjin Li

Papers

Circular RNA circ_0003028 contributes to tumorigenesis by regulating GOT2 via miR-1298-5p in non-small cell lung cancer.