Identification and experimental validation of G protein alpha inhibiting activity polypeptide 2 (GNAI2) as a microRNA-138 target in tongue squamous cell carcinoma

Content Provider	Semantic Scholar
Author	Jiang, Lu Dai, Yang Liu, Xiqiang Wang, Cheng Wang, Anxun Chen, Zujian Heidbreder, Caroline E. Kolokythas, Antonia Zhou, Xiaofeng
Copyright Year	2010
Abstract	MicroRNA deregulation is a critical event in tumor initiation and progression. The down-regulation of microRNA-138 has been frequently observed in various cancers, including tongue squamous cell carcinoma (TSCC). Our previous studies suggest that deregulation of miR-138 is associated with the enhanced proliferation and invasion in TSCC cells. Here, we seek to identify the targets of miR-138 in TSCC, and explore their functional relevance in tumorigenesis. Our genome-wide expression profiling experiments identified a panel of 194 unique transcripts that were significantly down-regulated in TSCC cells transfected with miR-138. A comprehensive screening using six different sequence-based microRNA target prediction algorithms revealed that 51 out of these 194 down-regulated transcripts are potential direct targets for miR-138. These targets include: chloride channel, nucleotide-sensitive, 1A (CLNS1A), G protein alpha inhibiting activity polypeptide 2 (GNAI2), solute carrier family 20, member 1 (SLC20A1), eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1), and Rho-related GTP-binding protein C (RhoC). GNAI2 is a known proto-oncogene that is involved in the initiation and progression of several different types of tumors. Direct targeting of miR-138 to two candidate binding sequences located in the 3′-untranslated region of GNAI2 mRNA was confirmed using luciferase reporter gene assays. Knockdown of miR-138 in TSCC cells enhanced the expression of GNAI2 at both mRNA and protein levels. In contrast, ectopic transfection of miR-138 reduced the expression of GNAI2, which, in consequence, led to reduced proliferation, cell cycle arrest and apoptosis. In summary, we identified a number of high-confident miR-138 target genes, including proto-oncogene GNAI2, which may play an important role in TSCC initiation and progression.
Starting Page	189
Ending Page	197
Page Count	9
File Format	PDF HTM / HTML
DOI	10.1007/s00439-010-0915-3
PubMed reference number	21079996
Journal	Medline
Volume Number	129
Alternate Webpage(s)	http://array.bioengr.uic.edu/~yangdai/pub/JDX2011.pdf
Alternate Webpage(s)	https://doi.org/10.1007/s00439-010-0915-3
Journal	Human Genetics
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article