Page 101 - Book of Abstracts
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th
                               8  Biannual Conference on Chemistry - CHEM 08

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

                      Marwa H. Soliman , Mohamed A. Ragheb , Emad M. Elzayat , Mervat S.
                                                                 1†
                                                                                    2
                                         1†
                          Mohamed , Nada El-Ekiaby , Ahmed I. Abdelaziz , Abdelhady A.
                                                       4
                                    1,3
                                                                             4
                                                    Abdelwahab   5,*
                      1 Department of Chemistry (Biochemistry Division), Faculty of Science, Cairo
                       University, Giza, Egypt.  Department of Zoology, Faculty of Science, Cairo
                                               2
                       University, Giza, Egypt.  Department of Biochemistry, Faculty of Science,
                                               3
                      University of Tabuk, Tabuk, Kingdom of Saudi Arabia.  School of Medicine,
                                                                            4
                      NewGiza University (NGU), NewGiza, Cairo, Egypt.  Department of Cancer
                                                                          5
                           Biology, National Cancer Institute, Cairo University, Cairo, Egypt.
                                     Email: abdelhady.abdelwahab@nci.cu.edu.eg.

                                                     ABSTRACT
                    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 miR-372-3p 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:  miR-372-3p  was markedly
                    downregulated in HepG2 cells compared with its normal control. We also 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: Taken together, 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: MiR-372-3p, Doxorubicin, Chemosensitivity, TACE, Mcl-1.





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