MicroRNA-21 induces resistance to 5-fluorouracil by down-regulating human DNA MutS homolog 2 (hMSH2)
作者： N. Valeri , P. Gasparini , C. Braconi , A. Paone , F. Lovat
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摘要: The overexpression of microRNA-21 (miR-21) is linked to a number human tumors including colorectal cancer, where it appears regulate the expression tumor suppressor genes p21, phosphatase and tensin homolog, TGFβ receptor II, B-cell leukemia/lymphoma 2 -associated X protein. Here we demonstrate that miR-21 targets down-regulates core mismatch repair (MMR) recognition protein complex, mutS homolog (hMSH2) 6 (hMSH6). Colorectal express high level display reduced hMSH2 expression. Cells overproduce exhibit significantly 5-fluorouracil (5-FU)-induced G2/M damage arrest apoptosis characteristic defects in MMR component. Moreover, xenograft studies dramatically reduces therapeutic efficacy 5-FU. These suggest down-regulation mutator gene associated with may be an important clinical indicator cancer.
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