MicroRNA-372-3p Predicts Response of TACE Patients Treated with Doxorubicin and Enhances Chemosensitivity in Hepatocellular Carcinoma
MicroRNA-372-3p Predicts Response of TACE Patients Treated with Doxorubicin and Enhances Chemosensitivity in Hepatocellular Carcinoma
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DOI：
10.2174/1871520620666200516145830
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发表时间：
2021-01-01
影响因子：
2.8
通讯作者：
Abdel-Wahab, Abdel-Hady A.
中科院分区：
文献类型：
--
作者：
Soliman, Marwa H.;Ragheb, Mohamed A.;Abdel-Wahab, Abdel-Hady A.
背景：确定检测和改善癌症化疗反应的因素是主要关注的问题. microRNA-372- 3 p（miR-372- 3 p）在包括肝细胞癌（HCC）在内的多种癌症的细胞增殖、凋亡和转移中发挥重要作用。目的：探讨miR-372- 3 p在肝癌细胞系HepG 2中增强阿霉素（Dox）化疗敏感性的作用。此外，还分析了miR-372- 3 p与接受经动脉化疗栓塞（TACE）和Dox治疗的HCC患者之间的相关性。通过在HepG 2细胞中转染miR-372- 3 p后的细胞活力、集落形成、凋亡和伤口愈合测定阐明了不同的细胞过程。已经通过定量实时PCR测定来估计用TACE/Dox治疗的原发性HCC患者的血液中的miR-372- 3 p水平。构建血清miR-372- 3 p的受试者工作曲线（ROC）分析以确定其预后意义。最后，Mcl-1的蛋白水平，抗凋亡的球员，已经使用western blot.Results进行了评估：我们发现一个显着更高的水平miR-372- 3 p的HCC患者的血液中的响应组接受TACE与Dox比非响应者。miR-372- 3 p的异位表达可抑制肝癌细胞的增殖、迁移和凋亡，并可诱导抗凋亡蛋白Mcl-1的表达减少。结论：miR-372- 3 p在肝癌中具有抑癌作用，可作为预测药物疗效的生物标志物。此外，该数据首次提到其在药物敏感性中的潜在作用，可能是HCC的治疗靶点。
Background: Identification of factors to detect and improve chemotherapy -response in cancer is the main concern. microRNA-372-3p (miR-372-3p) has been demonstrated to play a crucial role in cellular proliferation, apoptosis and metastasis of various cancers including Hepatocellular Carcinoma (HCC). However, its contribution towards Doxorubicin (Dox) chemosensitivity in HCC has never been studied.Objective: This study aims to investigate the potential role of miR-372-3p in enhancing Dox effects on HCC cell line (HepG2). Additionally, the correlation between miR-372-3p and HCC patients who received Transarterial Chemoembolization (TACE) with Dox treatment has been analyzed.Methods: Different cell processes were elucidated by cell viability, colony formation, apoptosis and wound healing assays after miR-372-3p transfection in HepG2 cells Furthermore, the miR-372-3p level has been estimated in the blood of primary HCC patients treated with TACE/Dox by quantitative real-time PCR assay. Receiver Operating Curve (ROC) analysis for serum miR-372-3p was constructed for its prognostic significance. Finally, the protein level of Mcl-1, the anti-apoptotic player, has been evaluated using western blot.Results: We found a significantly higher level of miR-372-3p in the blood of the responder group of HCC patients who received TACE with Dox than of non-responders. Ectopic expression of miR-372-3p reduced cell proliferation, migration and significantly induced apoptosis in HepG2 cells which was coupled with a decrease of anti-apoptotic protein Mcl-1.Conclusion: Our study demonstrated that miR-372-3p acts as a tumor suppressor in HCC and can act as a predictor biomarker for drug response. Furthermore, the data referred for the first time its potential role in drug sensitivity that might be a therapeutic target for HCC.