A new tumor suppressor LncRNA ADAMTS9-AS2 is regulated by DNMT1 and inhibits migration of glioma cells.
Growing number of long noncoding RNAs (lncRNAs) are emerging as new modulators in cancer origination and progression. A lncRNA, ADAM metallopeptidase with thrombospondin type 1 motif, 9 (ADAMTS9) antisense RNA 2 (ADAMTS9-AS2), with unknown function, is the antisense transcript of tumor suppressor ADAMTS9. In the present study, we investigated the expression pattern and functional role of ADAMTS9-AS2 in glioma by using real-time PCR and gain-/loss-of-function studies. The results showed that the ADAMTS9-AS2 expression was significantly downregulated in tumor tissues compared with normal tissues and reversely associated with tumor grade and prognosis. Multivariate analysis of the prognosis factors showed that low ADAMTS9-AS2 expression was a significant independent predictor of poor survival in glioma. Overexpression of ADAMTS9-AS2 resulted in significant inhibition of cell migration in glioma, whereas knockdown of ADAMTS9-AS2 showed the opposite effect. We also found that ADAMTS9-AS2 expression was negatively correlated with DNA methyltransferase-1 (DNMT1). In addition, DNMT1 knockdown led to remarkable enhancement of ADAMTS9-AS2 expression. By 5-aza-dC treatment, the ADAMTS9-AS2 expression was also reactivated. The results suggested that ADAMTS9-AS2 is a novel tumor suppressor modulated by DNMT1 in glioma. LncRNA ADAMTS9-AS2 may serve as a potential biomarker and therapeutic target for glioma.
Cancer Center, Chinese PLA General Hospital and Chinese PLA Medical School, Beijing, 100048, China.
Jie
J
Yao
Baosheng
B
Zhou
Jian
J
Zhang
Peiliang
P
Geng
Kang
K
Liu
Yunfeng
Y
Zhu
Weijie
W
Zhu
D051722:ADAM Proteins / Q000235:genetics / Q000502:physiology*; D000071119:ADAMTS9 Protein; D000328:Adult; D000368:Aged; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000502:physiology*; D000077209:Decitabine; D005260:Female; D005910:Glioma / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016372:RNA, Antisense / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000502:physiology*
D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D000077209:Decitabine; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; D051722:ADAM Proteins; D000071119:ADAMTS9 Protein; C412869:ADAMTS9 protein, human; D001374:Azacitidine