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Hsa-circRNA-G004213 通过调控肝癌中的 miR-513b-5p/PRPF39 促进顺铂敏感性。

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

机构信息

Department of Gastroenterology, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610000, P.R. China.

出版信息

Mol Med Rep. 2021 Jun;23(6). doi: 10.3892/mmr.2021.12060. Epub 2021 Apr 13.

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.

摘要

近年来,越来越多的证据证实,外泌体环状 RNA(circRNA)在肝癌(LC)的预后预测和诊断中发挥着关键作用。本研究比较了经动脉化疗栓塞(TACE)前后外泌体 circRNA 的表达模式。circRNA 测序分析在先行 TACE 组和第一次 TACE 术后组间鉴定出 390 个差异表达的 circRNA,在先行 TACE 组和第二次 TACE 术后组间鉴定出 489 个差异表达的 circRNA。差异表达 circRNA 的基因本体论分析表明,它们与脂肪酸代谢、受体结合和膜蛋白复合物有关。京都基因与基因组百科全书通路分析预测 TACE 后蛋白消化吸收通路被激活。筛选出一个新基因;hsa-circRNA-G004213(circ-G004213)在 TACE 后显著上调(倍数变化>10,P<0.01)。进一步分析发现 circ-G004213 显著增加了 HepG2 细胞对顺铂的敏感性,并与荷瘤小鼠的预后呈正相关。基于潜在的下游 miRNA 和 mRNAs,构建了 circRNA-miRNA-mRNA 网络。研究表明 circ-G004213 通过 miR-513b-5p/PRPF39 轴调节顺铂耐药性。最后,本研究证实 circ-G004213 与 TACE 后 LC 患者的预后呈正相关。因此,circ-G004213 可作为预测 TACE 疗效的指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c375/8025462/4507b4259b91/mmr-23-06-12060-g00.jpg

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