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Hsa‑circRNA‑G004213 promotes cisplatin sensitivity by regulating miR‑513b‑5p/PRPF39 in liver cancer.

ABSTRACT: In recent years, increasing evidence has confirmed that exosomal circular RNAs (circRNAs) serve a crucial role in the prognostic prediction and diagnosis of liver cancer (LC). The present study compared the expression patterns of exosomal circRNAs during transarterial chemoembolization (TACE). CircRNA sequencing analysis identified 390 differentially expressed circRNAs between the prior TACE and following the first TACE operation groups and 489 differentially expressed circRNAs between the prior to TACE and following the second TACE operation groups. Gene Ontology analysis of the differentially expressed circRNAs demonstrated that they were associated with fatty acid metabolism, receptor binding and membrane protein complexes. Kyoto Encyclopedia of Genes and Genomes pathway analysis predicted that protein digestion and absorption pathways were activated following TACE. A novel gene was screened out; hsa‑circRNA‑G004213 (circ‑G004213) was significantly upregulated following TACE (fold change >10, P < 0.01). Further analysis found circ‑G004213 significantly increased the cisplatin sensitivity of HepG2 cells and positively associated with the prognosis of tumor‑bearing mice. Based on the potential downstream miRNAs and mRNAs, the circRNA‑miRNA‑mRNA network was constructed. It was demonstrated that circ‑G004213 regulated cisplatin resistance via the miR‑513b‑5p/PRPF39 axis. Finally, the present study confirmed that circ‑G004213 was positively associated with the prognosis of patients with LC following TACE. Therefore, circ‑G004213 may be used as an indicator for predicting the efficacy of TACE.

SUBMITTER: Qin L

PROVIDER: S-EPMC8025462 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundOvarian cancer (OC) is a high-mortality gynecological cancer that is typically treated with cisplatin, although such treatment often results in chemoresistance. Ovarian cancer resistance is usually related to cell stemness. Herein, we explored the function of lncRNA WDFY3-AS2 in OC cell resistance to cisplatin (DDP).MethodsCisplatin resistant OC A2780 cell lines (A2780-DDP) were established by long-term exposure to cisplatin. CCK-8 assay were performed to evaluate the viability of A2780, and A2780-DDP cells. Quantitative RT-PCR was used to examine the expression of lncRNA WDFY3-AS2, miR-139-5p, and SDC4 in A2780-DDP cell lines. After treatment with cisplatin, cell apoptosis and CD44+CD166+-positive cells were measured by flow cytometry. The transwell assays were employed to measure the effect of WDFY3-AS2 on cell migration, and invasion. In addition, tumorsphere formation assay was used to enrich OC cancer stem cells (CSCs) from A2780-DDP cells. The expression of CSC markers (SOX2, OCT4, and Nanog) was detected by western blotting. The regulatory mechanism was confirmed by RNA pull down, and luciferase reporter assays. Furthermore, xenograft tumor in nude mice was used to assess the impact of WDFY3-AS2 on cisplatin resistance in OC in vivo.ResultsWDFY3-AS2 was highly expressed in OC A2780-DDP cells, and silencing WDFY3-AS2 significantly inhibited proliferation, migration and invasion but increased apoptosis in OC A2780-DDP cells. Additionally, WDFY3-AS2 significantly promoted the A2780-DDP cells tumorspheres. WDFY3-AS2 was predicted to impact OC by sponging miR-139-5p and regulating SDC4. The xenografts inoculated with A2780-DDP cells additionally confirmed that tumor growth in vivo was reduced by si-WDFY3-AS2 transfection. MiR-139-5p inhibitor or SDC4 overexpression could restore the suppressive influence of silenced WDFY3-AS2 on tumor growth.ConclusionsTogether, WDFY3-AS2 may lead to change of cisplatin resistance by the expression of miR-139-5p/SDC4 in the OC A2870-DDP cells both in vitro and in vivo. Our finding may provide a drug target for the drug resistance of OC.

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Hsa‑circRNA‑G004213 promotes cisplatin sensitivity by regulating miR‑513b‑5p/PRPF39 in liver cancer.

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