环状 RNA 内皮转录物 6 在肝细胞癌进展中充当致癌驱动因子。

CircETV6 acts as an oncogenic driver in hepatocellular carcinoma progression.

机构信息

Clinical Laboratory, Urumqi Maternal and Child Health Care Hospital, Urumqi, Xinjiang, China.

Department of Gynecology, Urumqi Maternal and Child Health Care Hospital, Urumqi, Xinjiang, China.

出版信息

J Biochem Mol Toxicol. 2024 Sep;38(9):e23766. doi: 10.1002/jbt.23766.

DOI:10.1002/jbt.23766

PMID:39215759

Abstract

Circular RNA (circRNA) plays important role in hepatocellular carcinoma (HCC) progression. However, the role and mechanism of circETV6 in HCC progression remain unclear. The levels of circETV6, ETV6, miR-383-5p, and PTPRE were tested by quantitative reverse-transcription polymerase chain reaction. Cell functions were assessed using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, 5-ethynyl-2'-deoxyuridine assay, colony formation assay, wound healing assay, transwell assay, and flow cytometry. The protein levels of poptosis-related markers and PTPRE were determined by western blot analysis. RNA interaction was analyzed by dual-luciferase reporter assay and RNA pull-down assay. A xenograft model was established to assess circETV6 roles in vivo. CircETV6 was highly expressed in HCC tissues and cells. CircETV6 knockdown repressed HCC cell proliferation, migration, invasion, and cell cycle, while accelerated apoptosis. CircETV6 targeted miR-383-5p, and miR-383-5p inhibition reversed the regulation of circETV6 knockdown on HCC cell progression. CircETV6 promoted PTPRE level via targeting miR-383-5p. Overexpressed PTPRE abolished the inhibition effect of miR-383-5p on HCC cell progression. In addition, circETV6 knockdown slowed HCC tumor growth in vivo. CircETV6 might facilitate HCC progression via the miR-383-5p/PTPRE axis, providing a novel target for HCC treatment.

摘要

环状 RNA（circRNA）在肝细胞癌（HCC）进展中发挥重要作用。然而，circETV6 在 HCC 进展中的作用和机制尚不清楚。通过定量逆转录聚合酶链反应检测 circETV6、ETV6、miR-383-5p 和 PTPRE 的水平。通过 3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2H-四唑溴盐（MTT）比色法、5-乙炔基-2'-脱氧尿苷（EdU）检测、集落形成实验、划痕实验、Transwell 实验和流式细胞术评估细胞功能。通过 Western blot 分析测定凋亡相关标志物和 PTPRE 的蛋白水平。通过双荧光素酶报告基因检测和 RNA 下拉实验分析 RNA 相互作用。建立异种移植模型评估 circETV6 在体内的作用。circETV6 在 HCC 组织和细胞中高表达。circETV6 敲低抑制 HCC 细胞增殖、迁移、侵袭和细胞周期，同时加速细胞凋亡。circETV6 靶向 miR-383-5p，miR-383-5p 抑制逆转了 circETV6 敲低对 HCC 细胞进展的调节。circETV6 通过靶向 miR-383-5p 促进 PTPRE 水平。过表达 PTPRE 消除了 miR-383-5p 对 HCC 细胞进展的抑制作用。此外，circETV6 敲低在体内减缓 HCC 肿瘤生长。circETV6 可能通过 miR-383-5p/PTPRE 轴促进 HCC 进展，为 HCC 治疗提供新的靶点。