Open AccessKITLG is a novel target of miR‐34c that is associated with the inhibition of growth and invasion in colorectal cancer cells
Author(s) -
Yang Shu,
Li Wenshuai,
Dong Fang,
Sun Haimei,
Wu Bo,
Tan Jun,
Zou Wanjing,
Zhou Deshan
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12368
Subject(s) - gene knockdown , gene silencing , cancer research , competing endogenous rna , chemistry , microrna , colorectal cancer , small interfering rna , hek 293 cells , cell culture , microbiology and biotechnology , rna , apoptosis , transfection , biology , long non coding rna , cancer , genetics , gene , biochemistry
MiR‐34c is considered a potent tumour suppressor because of its negative regulation of multiple target m RNA s that are critically associated with tumorigenesis and metastasis. In the present study, we demonstrated a novel target of miR‐34c , KITLG , which has been implicated in colorectal cancer ( CRC ). First, we found a significant negative relationship between miR‐34c and KITLG m RNA expression levels in CRC cell lines, including HT ‐29, HCT ‐116, SW 480 and SW 620 CRC cell lines. In silico analysis predicted putative binding sites for miR‐34c in the 3′ untranslated region (3′ UTR ) of KITLG m RNA . A dual‐luciferase reporter assay further confirmed that KITLG is a direct target of miR‐34c . Then, the cell lines were infected with lentiviruses expressing miR‐34c or a miR‐34c specific inhibitor. Restoration of miR‐34c dramatically reduced the expression of KITLG m RNA and protein, while silencing of endogenous miR‐34c increased the expression of KITLG protein. The miR‐34c ‐mediated down‐regulation of KITLG was associated with the suppression on proliferation, cellular transformation, migration and invasion of CRC cells, as well as the promotion on apoptosis. Knockdown of KITLG by its specific si RNA confirmed a critical role of KITLG down‐regulation for the tumour‐suppressive effects of miR‐34c in CRC cells. In conclusion, our results demonstrated that miR‐34c might interfere with KITLG ‐related CRC and could be a novel molecular target for CRC patients.