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

Author(s):

Marwa H. Soliman, Mohamed A. Ragheb, Emad M. Elzayat, Mervat S. Mohamed, Nada El-Ekiaby, Ahmed I. Abdelaziz and Abdel-Hady A. Abdel-Wahab*   Pages 246 - 253 ( 8 )

Abstract:

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. </p><p> 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. </p><p> 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. </p><p> 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. </p><p> 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.

Keywords:

MicroRNA-372-3p, doxorubicin, chemosensitivity, TACE, Mcl-1, hepatocellular carcinoma.

Affiliation:

Department of Chemistry (Biochemistry Division), Faculty of Science, Cairo University, Giza, Department of Chemistry (Biochemistry Division), Faculty of Science, Cairo University, Giza, Department of Zoology, Faculty of Science, Cairo University, Giza, Department of Chemistry (Biochemistry Division), Faculty of Science, Cairo University, Giza, School of Medicine, New Giza University (NGU), Cairo, School of Medicine, New Giza University (NGU), Cairo, Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo

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