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mi R ‐145 suppresses cell invasion in hepatocellular carcinoma cells: mi R ‐145 targets ADAM 17
Author(s) -
Yang Xuewei,
Zhang Longjuan,
Huang Xiaohui,
Chen Lianzhou,
Su Qiao,
Zeng Wentao,
Li Wen,
Wang Qian
Publication year - 2014
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.12152
Subject(s) - gene knockdown , hepatocellular carcinoma , metastasis , western blot , cancer research , transfection , cell growth , cell , microbiology and biotechnology , luciferase , cell culture , biology , chemistry , medicine , cancer , gene , biochemistry , genetics
Aim mi R ‐145 is a candidate tumor suppressor mi RNA . However, it is unknown whether mi R ‐145 is involved in the invasion of hepatocellular carcinoma ( HCC ). Therefore, we aimed to explore the effect and mechanism of mi R ‐145 in the control of HCC cell invasion. Methods HCC cell invasion was evaluated by transwell assays after transfection with pre‐mi R ‐145 or anti‐mi R ‐145. A luciferase reporter assay was used to determine whether a disintegrin and metalloprotease 17 ( ADAM 17) were a target of mi R ‐145. The levels of mi R ‐145 and ADAM 17 m RNA were detected by a real‐time polymerase chain reaction assay, and the level of ADAM 17 protein was measured by western blot analysis. Pearson's correlation test was used to assess the correlation between ADAM 17 m RNA expression and mi R ‐145 expression in 20 HCC tissue samples. Results mi R ‐145 was significantly downregulated in HCC tissues and cell lines. The loss of mi R ‐145 expression was associated with the tumor–node–metastasis stage, vascular invasion and intrahepatic metastasis. The overexpression of mi R ‐145 was able to suppress tumor MHCC‐97H cell invasion, whereas the knockdown of mi R ‐145 expression induced SMMC ‐7721 cell invasion. We demonstrated that mi R ‐145 bound directly to the 3′‐untranslated region of ADAM 17 and inhibited the expression of ADAM 17. The knockdown of ADAM 17 in SMMC ‐7721 cells could partially reverse the effects of anti‐mi R ‐145. mi R ‐145 expression was inversely associated with ADAM 17 expression in 20 HCC tissue specimens. Conclusion Our findings indicate that mi R ‐145 could inhibit HCC cell invasion by regulating the expression of ADAM 17.