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Downregulation of mi R ‐101 in gastric cancer correlates with cyclooxygenase‐2 overexpression and tumor growth
Author(s) -
He XiaoPu,
Shao Yun,
Li XiaoLin,
Xu Wei,
Chen GuoSheng,
Sun HuanHuan,
Xu HaiChen,
Xu Xian,
Tang Dan,
Zheng XiFeng,
Xue YiPing,
Huang GuoChang,
Sun WeiHao
Publication year - 2012
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.12013
Subject(s) - cancer , carcinogenesis , microrna , cancer research , downregulation and upregulation , metastasis , cell growth , tumor progression , biology , cancer cell , medicine , gene , biochemistry , genetics
Cyclooxygenase‐2 ( COX ‐2) plays an important role in the carcinogenesis and progression of gastric cancer. It has been demonstrated that COX ‐2 overexpression depends on different cellular pathways, involving both transcriptional and post‐transcriptional regulation. Micro RNA s (mi RNA s) are small, noncoding RNA s that function as post‐transcriptional regulators. Here, we characterize miR‐101 expression and its role in the regulation of COX ‐2 expression, which in turn, will provide us with additional insights into the potential therapeutic benefits of exogenous mi R ‐101 for treatment of gastric cancer. Our results showed that mi R ‐101 levels in gastric cancer tissues were significantly lower than those in the matched normal tissue ( P < 0.01). Furthermore, lower levels of mi R ‐101 were associated with increased tumor invasion and lymph node metastasis ( P < 0.05). We also found an inverse correlation between mi R ‐101 and COX ‐2 expression in both gastric cancer specimens and cell lines. Significant decreases in COX‐2 mRNA and COX ‐2 levels were observed in the pre‐mi R ‐101‐infected gastric cancer cells. One possible mechanism of interaction is that mi R ‐101 inhibited COX ‐2 expression by directly binding to the 3′‐ UTR of COX‐2 m RNA . Overexpression of mi R ‐101 in gastric cancer cell lines also inhibited cell proliferation and induced apoptosis in vitro , as well as inhibiting tumor growth in vivo . These results collectively indicate that mi R ‐101 may function as a tumor suppressor in gastric cancer, with COX‐2 as a direct target.