MicroRNA-373 (miR-373) post-transcriptionally regulates large tumor suppressor, homolog 2 (LATS2) and stimulates proliferation in human esophageal cancer.
LATS2 is a member of the LATS tumor suppressor family. It has been implicated in regulation of the cell cycle and apoptosis. Frequent loss of heterozygosity (LOH) of LATS2 has been reported in human esophageal cancer. But, the LATS2 gene expression and its regulatory mechanism in esophageal cancer remain unclear. The present study has shown that LATS2 protein expression was mediated by miR-373 at the post-transcriptional level and inversely correlated with miR-373 amounts in esophageal cancer cell lines. Furthermore, we demonstrated that the direct inhibition of LATS2 protein was mediated by miR-373 and manipulated the expression of miR-373 to affect esophageal cancer cells growth. Moreover, this correlation was supported by data collected ex vivo, in which esophageal cancer tissues from esophageal squamous cell carcinoma (ESCC) patients were analyzed. Finally, by miRNA microarray analysis, four miRNAs including miR-373 were over-expressed in ESCC samples. Our findings reveal that miR-373 would be a potential oncogene and it participates in the carcinogenesis of human esophageal cancer by suppressing LATS2 expression.
Lee
Kuen-Haur
KH
Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
Goan
Yih-Gang
YG
Hsiao
Michael
M
Lee
Chien-Hsing
CH
Jian
Shu-Huei
SH
Lin
Jen-Tai
JT
Chen
Yuh-Ling
YL
Lu
Pei-Jung
PJ
D049109:Cell Proliferation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
C527114:MIRN373 microRNA, human; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; C406449:LATS2 protein, human; D017346:Protein Serine-Threonine Kinases