Epigenetic modification of miR-141 regulates SKA2 by an endogenous 'sponge' HOTAIR in glioma.
Aberrant expression of miR-141 has recently implicated in the occurrence and development of various types of malignant tumors. However whether the involvement of miR-141 in the pathogenesis of glioma remains unknown. Here, we showed that miR-141 was markedly downregulated in glioma tissues and cell lines compared with normal brain tissues, and its expression correlated with the pathological grading. Enforced expression of miR-141 in glioma cells significantly inhibited cell proliferation, migration and invasion, whereas knockdown of miR-141 exerted opposite effect. Mechanistic investigations revealed that HOTAIR might act as an endogenous 'sponge' of miR-141, thereby regulating the derepression of SKA2. Further, we explored the molecular mechanism by which miR-141 expression was regulated, and found that the miR-141 promoter was hypermethylated and that promoter methylation of miR-141 was mediated by DNMT1 in glioma cells. Finally, both overexpression of miR-141 and knockdown of HOTAIR in a mouse model of human glioma resulted in significant reduction of tumor growth in vivo. Collectively, these results suggest that epigenetic modification of miR-141 and the interaction of ceRNA regulatory network will provide a new approach for therapeutics against glioma.
Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 230601, Hefei, China.|Cerebral Vascular Disease Research Center, Anhui Medical University, 230601, Hefei, China.
Er-Bao
EB
Bian
Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 230601, Hefei, China.|Cerebral Vascular Disease Research Center, Anhui Medical University, 230601, Hefei, China.
Chun-Chun
CC
Ma
Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 230601, Hefei, China.|Cerebral Vascular Disease Research Center, Anhui Medical University, 230601, Hefei, China.
Xiao-Jun
XJ
He
Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 230601, Hefei, China.|Cerebral Vascular Disease Research Center, Anhui Medical University, 230601, Hefei, China.
Chao
C
Wang
Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 230601, Hefei, China.|Cerebral Vascular Disease Research Center, Anhui Medical University, 230601, Hefei, China.
Gang
G
Zong
Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 230601, Hefei, China.|Cerebral Vascular Disease Research Center, Anhui Medical University, 230601, Hefei, China.
Hong-Liang
HL
Wang
Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 230601, Hefei, China.|Cerebral Vascular Disease Research Center, Anhui Medical University, 230601, Hefei, China.
Bing
B
Zhao
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000235:genetics
D020413:3' Untranslated Regions; D002868:Chromosomal Proteins, Non-Histone; C561566:HOTAIR long untranslated RNA, human; C533895:MIRN141 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; C516428:SKA2 protein, human
DNMT1; HOTAIR; SKA2; gliomas; miR-141