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Micro RNA ‐503 suppresses proliferation and cell‐cycle progression of endometrioid endometrial cancer by negatively regulating cyclin D 1
Author(s) -
Xu YanYing,
Wu HuiJuan,
Ma HongDa,
Xu LiPing,
Huo Yan,
Yin LiRong
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12365
Subject(s) - cell cycle , ectopic expression , biology , cancer research , microrna , cyclin d1 , oncogene , cell growth , endometrial cancer , cell , microbiology and biotechnology , cancer , cell culture , gene , genetics
Micro RNA s (mi RNA s) are post‐transcriptional inhibitor regulators of gene expression that act by directly binding complementary m RNA and are key determinants of cancer initiation and progression. In this study, we revealed a role for the tumor‐suppressor miRNA miR‐503 in endometrioid endometrial cancer ( EEC ) cells. The miR‐503 expression level gradually decreases across normal endometrial tissues, endometrial tissues with complex atypical hyperplasia, and EEC tissues. A relatively high level of miR‐503 in EEC tissues indicates a longer survival time in EEC patients. The expression of a cell cycle‐associated oncogene encoding cyclin D1 ( CCND 1) was inversely correlated with miR‐503 expression in EEC tissues and cell lines. CCND 1 has a binding sequence of miR‐503 within its 3′ untranslated region, and was confirmed to be a direct target of miR‐503 by the fluorescent reporter assays. Increasing the miR‐503 level in EEC cells suppressed cell viability, colon formation activity and cell‐cycle progression, and the inhibited oncogenic phenotypes induced by miR‐503 were alleviated by ectopic expression of CCND 1 without the untranslated region sequence. Furthermore, in vivo studies also suggested a suppressive effect of miR‐503 on EEC cell‐derived xenografts. miR‐503 increased in cell cycle‐arrested EEC cells, and was restored to a normal level in EEC cells after cell cycle re‐entry, while CCND 1 displayed the opposite expression pattern. Collectively, this study suggested that miR‐503 plays a tumor‐suppressor role by targeting CCND 1. Abnormal suppression of miR‐503 leads to an increase in the CCND 1 level, which may promote carcinogenesis and progression of EEC .