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Involvement of micro RNA ‐224 in cell proliferation, migration, invasion, and anti‐apoptosis in hepatocellular carcinoma
Author(s) -
Zhang Yizhou,
Takahashi Shoichi,
Tasaka Akiko,
Yoshima Tadahiko,
Ochi Hidenori,
Chayama Kazuaki
Publication year - 2013
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2012.07271.x
Subject(s) - gene expression , cancer research , microbiology and biotechnology , rna , microrna , apoptosis , cell growth , gene , hepatocellular carcinoma , microarray , microarray analysis techniques , biology , medicine , genetics
Abstract Background and Aim Changes in micro RNA (mi RNA ) expression have been detected in a broad range of biological processes including cancer. Here we determined the role of mi RNA dysregulation in hepatocellular carcinoma ( HCC ). Methods We investigated the expression of nine cancer‐related mi RNA s in HCC . Among these, mi R ‐224 was the most significantly uprgulated in HCC tissues ( n = 18), compared with normal ( n = 9) and HCC adjacent non‐tumorous liver tissues ( n = 18). After leading‐in currently reported gene targets from S anger mi RB ase, we characterized the expression profiles of target genes of mi R ‐224 using c DNA microarray. The altered expression was subsequently validated by real‐time polymerase chain reaction and W estern blot. The phenotypic changes by mi R ‐224 expression were identified by cell viability, apoptosis, and in vitro scratch assays. Results The microarray analysis and mi RNA target prediction analysis allowed the identification of significant changes in 68 putative gene targets after overexpression of mi R ‐224. The high‐ranking genes CDC 42, CDH 1, PAK 2, BCL ‐2, and MAPK 1 were confirmed as important targets of mi R ‐224 and involvement in hepatocarcinogenesis. Overexpression of mi R ‐224 significantly in H ek293 and H uh7 cells altered the expression levels of CDC 42, CDH 1, PAK 2, and BCL ‐2 at both m RNA and protein levels. Similar changes in the expression of the same genes were also observed in HCC tissues. Via functional analyses, cell proliferation, migration and anti‐apoptosis were proved to be affected by mi R ‐224 expression. Conclusion The results suggest that mi R ‐224 plays a role in cell proliferation, migration, invasion, and anti‐apoptosis in HCC by directly binding to its gene targets, implicating this RNA in HCC development and progression.