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MicroRNA‐21 increases the resistance to CDDP in Hela cervical carcinoma cells by targeting PDCD4 and MSH2
Author(s) -
Cheng JiaoYing,
Nishi Hirotaka,
Yonekawa Chinatsu,
Takara Kohji,
Isaka Keiichi
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb576
Subject(s) - hela , microrna , luciferase , cancer research , transfection , microbiology and biotechnology , western blot , msh2 , cisplatin , biology , chemistry , cell culture , cancer , colorectal cancer , gene , dna mismatch repair , chemotherapy , biochemistry , genetics
Objectives MicroRNA‐21 (miR‐21) has been found to be over‐expressed in many human cancers, including cervical cancer. Our aim is to investigate the association of miR‐21 with the chemosensitivity of HeLa cervical carcinoma cells to cis‐Diaminedichloroplatinum (CDDP). Methods With cervical carcinoma cell lines, HeLa and CDDP‐resistant HeLa (HeLa/CDDP), the cell growth was examined by MTT assays with miR‐21 or miR‐21 inhibitor transfection. TaqMan RT‐PCR was performed to detect the miR‐21 and mRNA expression of Programmed Cell Death 4 (PDCD4) and mutS homolog 2, colon cancer, nonpolyposis type 1 (MSH2). The protein expression of PDCD4 and MSH2 was detected with western blot assay. Luciferase assay was performed to analyze the potential targets of miR‐21. Results Cell growth results suggested miR‐21 inhibitor inhibit CDDP‐resistant HeLa growth significantly. Compared with HeLa, MiR‐21 and mRNA of PDCD4 and MSH2 expression in HeLa/CDDP were higher, but the protein expression of PDCD4 and MSH2 in HeLa/CDDP were downregulated in western blot results. Transfection of miR‐21 inhibitor for HeLa/CDDP with PDCD4 3′ untranslated region (3′ UTR) or MSH2 3′UTR vector showed significant increase in luciferase activity compared with control. Conclusions Over‐expression of miR‐21 may play critical roles for the CDDP‐resistance in cervical cancer, at least in part via targeting PDCD4 and MSH2.