KITLG is a novel target of miR‐34c that is associated with the inhibition of growth and invasion in colorectal cancer cells. Issue 10 (12th September 2014)

• Record Type: Journal Article
• Authors: Yang, Shu; Li, Wen‐shuai; Dong, Fang; Sun, Hai‐mei; Wu, Bo; Tan, Jun; Zou, Wan‐jing; Zhou, De‐shan
• Is Part Of: Journal of cellular and molecular medicine. Volume 18:Issue 10(2014)
• Page Start: 2092
• Page End: 2102
• Publication Date: 2014-09-12
• Subjects: Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.12368
• Languages: English
• ISSNs: 1582-1838

Abstract

<abstract abstract-type="main" id="jcmm12368-abs-0001"> <title>Abstract</title> <p> <italic>MiR‐34c</italic> is considered a potent tumour suppressor because of its negative regulation of multiple target mRNAs that are critically associated with tumorigenesis and metastasis. In the present study, we demonstrated a novel target of <italic>miR‐34c</italic>, KITLG, which has been implicated in colorectal cancer (CRC). First, we found a significant negative relationship between <italic>miR‐34c</italic> and <italic>KITLG</italic> mRNA expression levels in CRC cell lines, including HT‐29, HCT‐116, SW480 and SW620 CRC cell lines. <italic>In silico</italic> analysis predicted putative binding sites for <italic>miR‐34c</italic> in the 3′ untranslated region (3′UTR) of <italic>KITLG</italic> mRNA. A dual‐luciferase reporter assay further confirmed that <italic>KITLG</italic> is a direct target of <italic>miR‐34c</italic>. Then, the cell lines were infected with lentiviruses expressing <italic>miR‐34c</italic> or a <italic>miR‐34c</italic> specific inhibitor. Restoration of <italic>miR‐34c</italic> dramatically reduced the expression of <italic>KITLG</italic> mRNA and protein, while silencing of endogenous <italic>miR‐34c</italic> increased the expression of KITLG protein. The <italic>miR‐34c</italic>‐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 siRNA confirmed a critical role of KITLG down‐regulation for the tumour‐suppressive effects of <italic>miR‐34c</italic> in CRC cells. In conclusion, our results demonstrated that <italic>miR‐34c</italic> might interfere with KITLG‐related CRC and could be a novel molecular target for CRC patients.</p> </abstract>