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Micro‐RNA‐21 regulates TGF‐β‐induced myofibroblast differentiation by targeting PDCD4 in tumor‐stroma interaction
Author(s) -
Yao Qin,
Cao Siyu,
Li Chun,
Mengesha Asferd,
Kong Beihua,
Wei Mingqian
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25506
Subject(s) - myofibroblast , transdifferentiation , downregulation and upregulation , transforming growth factor , stroma , microbiology and biotechnology , microrna , cancer research , stromal cell , biology , fibroblast , pathology , cell culture , immunology , fibrosis , gene , stem cell , medicine , genetics , immunohistochemistry
Transforming growth factor‐β1 (TGF‐β1) induces stromal fibroblast‐to‐myofibroblast transdifferentiation in the tumor‐stroma interactive microenvironment via modulation of multiple phenotypic and functional genes, which plays a critical role in tumor progression. Up to now, the involvement of micro‐RNAs (miRNAs) and their roles in TGF‐β1‐induced myofibroblast differentiation in tumor‐stroma interaction are unclear. Using quantitative real‐time RT‐PCR, we demonstrated that the expression of micro‐RNA‐21 (miR‐21) was upregulated in activated fibroblasts after treatment with TGF‐β1 or conditioned medium from cancer cells. To determine the potential roles of miR‐21 in TGF‐β1‐mediated gene regulation during myofibroblast conversion, we showed that miR‐21 expression was downregulated by miR‐21 inhibitor and upregulated by miR‐21 mimic. Interestingly, downregulation of miR‐21 with the inhibitor effectively inhibited TGF‐β1‐induced myofibroblast differentiation while upregulation of miR‐21 with a mimic significantly promoted myofibroblast differentiation. We further demonstrated that MiR‐21 directly targeted and downregulated programmed cell death 4 ( PDCD4 ) gene, which in turn acted as a negative regulator of several phenotypic and functional genes of myofibroblasts. Taken together, these results suggested that miR‐21 participated in TGF‐β1‐induced myofibroblast transdifferentiation in cancer stroma by targeting PDCD4 .