Department of Infectious Disease, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan City, Shanxi Province, China.
Anticancer Drugs. 2022 Feb 1;33(2):167-177. doi: 10.1097/CAD.0000000000001258.
Hepatocellular carcinoma (HCC) is a major world public problem in the world, with high morbidity and mortality rates. Circular RNA (circRNA) circ_0073181 has been reported to be related to HCC development. However, the mechanism of circ_0073181 in HCC is far from being addressed. Circ_0073181, microRNA-548p (miR-548p) and protein tyrosine phosphatase receptor type E (PTPRE) level were detected by real-time quantitative PCR (RT-qPCR). Cell proliferation, migration, invasion and apoptosis were detected by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine, wound healing, transwell and flow cytometry assay. Protein levels of proliferating cell nuclear antigen, Bcl-2 related X protein (Bax) and PTPRE were examined by western blot assay. The binding relationship between miR-548p and circ_0073181 or PTPRE was predicted by circular RNA interactome and targetScan and then verified by a dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The biologic role of circ_0073181 on HCC tumor growth was examined by the xenograft tumor model in vivo. Circ_0073181 and PTPRE were upregulated, and miR-548p was decreased in HCC tissues and cells. Furthermore, circ_0073181 knockdown could boost proliferation, migration, invasion and repress apoptosis of HCC cells in vitro. The mechanical analysis suggested that circ_0073181 could regulate PTPRE expression by sponging miR-548p. In addition, circ_0073181 knockdown suppressed cell growth of HCC in vivo. Circ_0073181 silencing could inhibit HCC cell growth and metastasis partly by regulating the miR-548p/ PTPRE axis, providing a promising therapeutic target for the HCC treatment.
肝细胞癌（HCC）是全球主要的公共卫生问题之一，具有高发病率和死亡率。环状 RNA（circRNA）circ_0073181 已被报道与 HCC 的发展有关。然而，circ_0073181 在 HCC 中的作用机制仍远未得到解决。通过实时定量 PCR（RT-qPCR）检测 circ_0073181、微小 RNA-548p（miR-548p）和蛋白酪氨酸磷酸酶受体 E（PTPRE）的水平。通过细胞计数试剂盒-8（CCK-8）、5-乙炔基-2'-脱氧尿苷、划痕愈合、Transwell 和流式细胞术检测细胞增殖、迁移、侵袭和凋亡。通过 Western blot 检测增殖细胞核抗原、Bcl-2 相关 X 蛋白（Bax）和 PTPRE 的蛋白水平。通过环状 RNA 相互作用组和靶标扫描预测 miR-548p 与 circ_0073181 或 PTPRE 的结合关系，然后通过双荧光素酶报告基因和 RNA 免疫沉淀（RIP）实验验证。通过体内异种移植肿瘤模型研究 circ_0073181 对 HCC 肿瘤生长的生物学作用。circ_0073181 和 PTPRE 在 HCC 组织和细胞中上调，而 miR-548p 下调。此外，circ_0073181 敲低可促进 HCC 细胞体外增殖、迁移、侵袭和抑制凋亡。力学分析表明，circ_0073181 通过海绵吸附 miR-548p 调节 PTPRE 表达。此外，circ_0073181 敲低抑制 HCC 细胞在体内的生长。circ_0073181 沉默可部分通过调节 miR-548p/PTPRE 轴抑制 HCC 细胞生长和转移，为 HCC 治疗提供了有前途的治疗靶点。
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