Title:MicroRNA-372-3p Predicts Response of TACE Patients Treated with Doxorubicin and Enhances Chemosensitivity in Hepatocellular Carcinoma
VOLUME: 21 ISSUE: 2
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*
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
Keywords:MicroRNA-372-3p, doxorubicin, chemosensitivity, TACE, Mcl-1, hepatocellular carcinoma.
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.
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.
