miR-372 regulates cell cycle and apoptosis of ags human gastric cancer cell line through direct regulation of LATS2.
Previously, we have reported tissue- and stage-specific expression of miR-372 in human embryonic stem cells and so far, not many reports speculate the function of this microRNA (miRNA). In this study, we screened various human cancer cell lines including gastric cancer cell lines and found first time that miR-372 is expressed only in AGS human gastric adenocarcinoma cell line. Inhibition of miR-372 using antisense miR-372 oligonucleotide (AS-miR-372) suppressed proliferation, arrested the cell cycle at G2/M phase, and increased apoptosis of AGS cells. Furthermore, AS-miR-372 treatment increased expression of LATS2, while over-expression of miR-372 decreased luciferase reporter activity driven by the 3' untranslated region (3' UTR) of LATS2 mRNA. Over-expression of LATS2 induced changes in AGS cells similar to those in AGS cells treated with AS-miR-372. Taken together, these findings demonstrate an oncogenic role for miR-372 in controlling cell growth, cell cycle, and apoptosis through down-regulation of a tumor suppressor gene, LATS2.
Cho
Wha Ja
WJ
Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-060, Korea.
Shin
Jeong Min
JM
Kim
Jong Soo
JS
Lee
Man Ryul
MR
Hong
Ki Sung
KS
Lee
Jun-Ho
JH
Koo
Kyoung Hwa
KH
Park
Jeong Woo
JW
Kim
Kye-Seong
KS
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D035683:MicroRNAs; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; C406449:LATS2 protein, human; D017346:Protein Serine-Threonine Kinases