Format

Send to

Choose Destination
RNA Biol. 2014;11(7):845-54. doi: 10.4161/rna.29356. Epub 2014 Jun 12.

Identification of miRNAs that specifically target tumor suppressive KLF6-FL rather than oncogenic KLF6-SV1 isoform.

Author information

1
Croucher Laboratory for Human Genomics, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, P.R. China; School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, P.R. China.
2
School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, P.R. China.
3
Department of Clinical Laboratory, Nanshan Affiliated Hospital of Guangdong Medical College, Shenzhen, 518052, P.R. China.
4
Guangzhou Institute of Advanced Technology, Chinese Academy of Sciences, Guangzhou, 510000, P.R. China.
5
Department of Gastroenterology, Hebei Key Laboratory of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 230000, P.R. China.

Abstract

The Krüppel like factor 6 (KLF6) gene encodes multiple protein isoforms derived from alternative mRNA splicing, most of which are intimately involved in hepatocarcinogenesis and tumor progression. Recent bioinformatics analysis shows that alternative mRNA splicing of the KLF6 gene produces around 16 alternatively spliced variants with divergent or even opposing functions. Intriguingly, the full-length KLF6 (KLF6-FL) is a tumor suppressor gene frequently inactivated in liver cancer, whereas KLF6 splice variant 1 (KLF6-SV1) is an oncogenic isoform with antagonistic function against KLF6-FL. Compelling evidence indicates that miRNA, the small endogenous non-coding RNA (ncRNA), acts as a vital player in modulating a variety of cellular biological processes through targeting different mRNA regions of protein-coding genes. To identify the potential miRNAs specifically targeting KLF6-FL, we utilized bioinformatics analysis in combination with the luciferase reporter assays and screened out two miRNAs, namely miR-210 and miR-1301, specifically targeted the tumor suppressive KLF6-FL rather than the oncogenic KLF6-SV1. Our in vitro experiments demonstrated that stable expression of KLF6-FL inhibited cell proliferation, migration and angiogenesis while overexpression of miR-1301 promoted cell migration and angiogenesis. Further experiments demonstrated that miR-1301 was highly expressed in liver cancer cell lines as well as clinical specimens and we also identified the potential methylation and histone acetylation for miR-1301 gene. To sum up, our findings unveiled a novel molecular mechanism that specific miRNAs promoted tumorigenesis by targeting the tumor suppressive isoform KLF6-FL rather than its oncogenic isoform KLF6-SV1.

KEYWORDS:

Alternative splicing; KLF6; miRNA

PMID:
24921656
PMCID:
PMC4179959
DOI:
10.4161/rna.29356
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Taylor & Francis Icon for PubMed Central
Loading ...
Support Center