MiR-­‐372-3p Predicts Response of TACE Patients Treated with Doxorubicin and Enhances Chemosensitivity in Hepatocellular Carcinoma

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Author(s): Marwa H. Soliman, Mohamed A. Ragheb, Emad M. Elzayat, Mervat S. Mohamed, Nada El-Ekiaby, Ahmed I. Abdelaziz, Abdelhady A. Abdelwahab*

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

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Background: Identification of factors to detect and improve chemotherapy‐response in cancer is a 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). Their correlation has been additionally analyzed for HCC patients who received Transarterial Chemoembolization (TACE) with Dox treatment.

Methods: Different cell processes were elucidated by cell viability, colony formation, apoptosis and wound healing assays after miR372-3p transfection in HepG2 cells Furthermore, miR-372-3p level has been estimated in 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, protein level of Mcl-1, the anti-apoptotic player, has been evaluated using western blot.

Results: We found a significant higher level of miR-372-3p in blood of responder group of HCC patients 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 decreased of anti-apoptotic protein Mcl-1.

Conclusion: Our study demonstrated that miR-372-3p acts as 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.

Keywords: microRNA-372-3p, doxorubicin, chemosensitivity, Transarterial Chemoembolization (TACE), Myeloid cell leukemia 1(Mcl-1), hepatocellular carcinoma.

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(E-pub Ahead of Print)
DOI: 10.2174/1871520620666200516145830
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