title: miR-372 regulates glioma cell proliferation and invasion by directly targeting PHLPP2.
abstract: MicroRNAs are known to be involved in carcinogenesis and tumor progression in glioma. Recently, microRNA-372 (miR-372) has been proved to play a substantial role in several human cancers, but its functions in glioma remain unclear. In this study, we confirmed that miR-372 was commonly upregulated in glioma cell lines and tissues. Downregulation of miR-372 markedly inhibited cell proliferation and invasion and induced G1/S arrest and apoptosis. Consistently, the xenograft mouse model also unveiled the suppressive effects of miR-372 knockdown on tumor growth. Further studies revealed that miR-372 modulated the expression of PHLPP2 by directly targeting its 3'-untranslated region (3'-UTR) and that miR-372 expression was inversely correlated with PHLPP2 expression in glioma samples. Silencing of PHLPP2 could rescue the inhibitory effect of miR-372 inhibitor. Moreover, miR-372 knockdown suppressed the phosphorylation levels of the major components of PI3K/Akt pathway including Akt, mTOR, and P70S6K. Taken together, our results suggest that miR-372 functions as an oncogenic miRNA through targeting PHLPP2 in glioma.
authors.affiliation: Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Bin
authors.initials: B
authors.lastname: Hao
authors.forename: Guosheng
authors.initials: G
authors.lastname: Han
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Dongwei
authors.initials: D
authors.lastname: Dai
authors.forename: Yanan
authors.initials: Y
authors.lastname: Li
authors.forename: Xi
authors.initials: X
authors.lastname: Wu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhou
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Yue
authors.forename: Laixing
authors.initials: L
authors.lastname: Wang
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Cao
authors.forename: Jianmin
authors.initials: J
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C561021:MIRN372 microRNA, human; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C541572:PHLPP2 protein, human; D010749:Phosphoprotein Phosphatases
keywords: GLIOMA; INVASION; PHLPP2; PROLIFERATION; miR-372