CircROBO1 knockdown improves the radiosensitivity of hepatocellular carcinoma by regulating RAD21

IF 3.7 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology Pub Date : 2024-08-14 DOI:10.1016/j.aohep.2024.101536

Kai Yang , Yanpeng Ding , Jun Han , Rui He

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Abstract

Introduction and Objectives

Radioresistance is a common problem in the treatment of many cancers, including hepatocellular carcinoma (HCC). Previous studies have shown that circROBO1 is highly expressed in HCC tissues and acts as a cancer promoter to accelerate the malignant progression of HCC. However, the role and mechanism of circROBO1 in HCC radioresistance remain unclear.

Materials and Methods

CircROBO1, microRNA (miR)-136-5p and RAD21 expression levels were analyzed by quantitative real-time PCR. Cell function and radioresistance were evaluated by colony formation assay, cell counting kit 8 assay, EdU assay and flow cytometry. Protein expression was determined using western blot analysis. RNA interaction was analyzed by dual-luciferase reporter assay and RNA pull-down assay. In vivo experiments were performed by constructing mice xenograft models.

Results

CircROBO1 was highly expressed in HCC, and its knockdown inhibited HCC cell proliferation and promoted apoptosis to enhance cell radiosensitivity. On the mechanism, circROBO1 could serve as miR-136-5p sponge to positively regulate RAD21. MiR-136-5p inhibitor or RAD21 overexpression reversed the regulation of circROBO1 knockdown on the radiosensitivity of HCC cells. Also, circROBO1 interference improved the radiosensitivity of HCC tumors in vivo.

Conclusions

CircROBO1 might be a promising target for treating HCC radioresistance.

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CircROBO1基因敲除通过调节RAD21提高肝细胞癌的放射敏感性

引言和目的：放射耐药性是包括肝细胞癌（HCC）在内的许多癌症治疗中的常见问题。先前的研究表明，circROBO1 在 HCC 组织中高表达，并作为癌症启动子加速 HCC 的恶性进展。然而，circROBO1在HCC放射抗性中的作用和机制仍不清楚：通过实时定量 PCR 分析 CircROBO1、microRNA (miR)-136-5p 和 RAD21 的表达水平。通过集落形成试验、细胞计数试剂盒 8 试验、EdU 试验和流式细胞术评估细胞功能和放射抗性。蛋白质表达采用 Western 印迹分析法测定。通过双荧光素酶报告实验和 RNA 下拉实验分析 RNA 相互作用。通过构建小鼠异种移植模型进行体内实验：结果：CircROBO1在HCC中高表达，敲除CircROBO1可抑制HCC细胞增殖，促进细胞凋亡，增强细胞的放射敏感性。在机制上，circROBO1可作为miR-136-5p海绵对RAD21进行正向调节。MiR-136-5p抑制剂或RAD21过表达可逆转circROBO1敲除对HCC细胞辐射敏感性的调控。同时，circROBO1干扰也改善了HCC肿瘤在体内的放射敏感性：CircROBO1可能是治疗HCC放射抗性的一个有前景的靶点。

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来源期刊

Annals of hepatology 医学-胃肠肝病学

CiteScore

7.90

自引率

2.60%

发文量

183

审稿时长

4-8 weeks

期刊介绍： Annals of Hepatology publishes original research on the biology and diseases of the liver in both humans and experimental models. Contributions may be submitted as regular articles. The journal also publishes concise reviews of both basic and clinical topics.