Dataset Information

Circular RNA circ_0026359 Enhances Cisplatin Resistance in Gastric Cancer via Targeting miR-1200/POLD4 Pathway.

ABSTRACT: Human gastric cancer is one of the most common malignant tumors with a poor prognosis. Cisplatin (CDDP) is a well-known first-line chemotherapeutic drug. Acquired resistance retards the clinical application of CDDP in gastric cancer. In this study, circular RNA circ_0026359 was demonstrated to be overexpressed in gastric cancer tissues/cells compared with normal gastric tissues/cells and was overexpressed in CDDP-resistant gastric cancer tissues/cells compared with CDDP-sensitive gastric cancer tissues/cells. High levels of circ_0026359 were associated with low overall survival (OS) and relapse-free survival (RFS) rates in gastric cancer patients. circ_0026359 was examined to promote CDDP resistance in gastric cancer cells. circ_0026359 directly interacted and negatively regulated miR-1200. POLD4 was a direct target of miR-1200. miR-1200/POLD4 pathway mediated the promoting role of circ_0026359 in CDDP resistance of gastric cancer. circ_0026359 could be used as a potential target for CDDP-resistant gastric cancer therapy.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC7443216 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Circular RNA circ_0026359 Enhances Cisplatin Resistance in Gastric Cancer via Targeting miR-1200/POLD4 Pathway.

Zhang Zongyao Z Yu Xin X Zhou Bo B Zhang Jiajia J Chang Jiacong J

BioMed research international 20200813

Human gastric cancer is one of the most common malignant tumors with a poor prognosis. Cisplatin (CDDP) is a well-known first-line chemotherapeutic drug. Acquired resistance retards the clinical application of CDDP in gastric cancer. In this study, circular RNA circ_0026359 was demonstrated to be overexpressed in gastric cancer tissues/cells compared with normal gastric tissues/cells and was overexpressed in CDDP-resistant gastric cancer tissues/cells compared with CDDP-sensitive gastric cancer ...[more]

PMID: 32855967

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Project description:Background: Cisplatin is the first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC), and emerging evidences suggests that targeting circular RNAs (circRNAs) is an effective strategy to increase cisplatin-sensitivity in NSCLC, but the detailed mechanisms are still not fully delineated.Methods: Cell proliferation, viability and apoptosis were examined by using the cell counting kit-8 (CCK-8) assay, trypan blue staining assay and Annexin V-FITC/PI double staining assay, respectively. The expression levels of cancer associated genes were measured by using the Real-Time qPCR and Western Blot analysis at transcriptional and translated levels. Dual-luciferase reporter gene system assay was conducted to validated the targeting sites among hsa_circRNA_103809, miR-377-3p and 3' untranslated region (3'UTR) of GOT1 mRNA. The expression status, including expression levels and localization, were determined by immunohistochemistry (IHC) assay in mice tumor tissues.Results: Here we identified a novel hsa_circRNA_103809/miR-377-3p/GOT1 signaling cascade which contributes to cisplatin-resistance in NSCLC in vitro and in vivo. Mechanistically, parental cisplatin-sensitive NSCLC (CS-NSCLC) cells were subjected to continuous low-dose cisplatin treatment to generate cisplatin-resistant NSCLC (CR-NSCLC) cells, and we found that hsa_circRNA_103809 and GOT1 were upregulated, while miR-377-3p was downregulated in CR-NSCLC cells but not in CS-NSCLC cells. In addition, hsa_circRNA_103809 sponged miR-337-3p to upregulate GOT1 in CS-NSCLC cells, and knock-down of hsa_circRNA_103809 enhanced the inhibiting effects of cisplatin on cell proliferation and viability, and induced cell apoptosis in CR-NSCLC cells, which were reversed by downregulating miR-377-3p and overexpressing GOT1. Consistently, overexpression of hsa_circRNA_103809 increased cisplatin-resistance in CS-NSCLC cells by regulating the miR-377-3p/GOT1 axis. Finally, silencing of hsa_circRNA_103809 aggravated the inhibiting effects of cisplatin treatment on NSCLC cell growth in vivo.Conclusions: Analysis of data suggested that targeting the hsa_circRNA_103809/miR-377-3p/GOT1 pathway increased susceptibility of CR-NSCLC cells to cisplatin, and this study provided novel targets to improve the therapeutic efficacy of cisplatin for NSCLC treatment in clinic.

Project description:BackgroundChemoresistance is one of the major obstacles for cancer therapy in the clinic. Circular RNAs (circRNAs) are involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC) and chemoresistance. This study aimed to explore the role and molecular mechanism of circ_0006168 in Taxol resistance of ESCC.MethodsThe expression levels of circ_0006168, microRNA-194-5p (miR-194-5p) and jumonji domain containing 1C (JMJD1C) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The half-inhibition concentration (IC50) value of Taxol was evaluated by Cell Counting Kit-8 (CCK-8) assay. Cell proliferation was evaluated by CCK-8 and colony formation assays. Cell migration and invasion were detected by transwell assay. Cell apoptosis was determined by flow cytometry. The interaction between miR-194-5p and circ_0006168 or JMJD1C was predicted by bioinformatics analysis (Circinteractome and TargetScan) and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) and RNA pull-down assays. The mice xenograft model was established to investigate the roles of circ_0006168 in vivo.ResultsCirc_0006168 and JMJD1C were upregulated and miR-194-5p was downregulated in ESCC tissues, ESCC cells, and Taxol-resistant cells. Functionally, knockdown of circ_0006168 or JMJD1C increased Taxol sensitivity of ESCC in vitro via inhibiting cell proliferation, migration and invasion, and promoting apoptosis. Moreover, circ_0006168 could directly bind to miR-194-5p and JMJD1C was verified as a direct target of miR-194-5p. Mechanically, circ_0006168 was a sponge of miR-194-5p to regulate JMJD1C expression in ESCC cells. Furthermore, JMJD1C overexpression reversed the promotive effect of circ_0006168 knockdown on Taxol sensitivity. Besides, circ_0006168 silence suppressed tumor growth in vivo.ConclusionCirc_0006168 facilitated Taxol resistance in ESCC by regulating miR-194-5p/JMJD1C axis, providing a promising therapeutic target for ESCC chemotherapy.

Dataset Information

Circular RNA circ_0026359 Enhances Cisplatin Resistance in Gastric Cancer via Targeting miR-1200/POLD4 Pathway.

Publications

Circular RNA circ_0026359 Enhances Cisplatin Resistance in Gastric Cancer via Targeting miR-1200/POLD4 Pathway.

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