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.

The aberrantly expressed miR-372 partly impairs sensitivity to apoptosis in parathyroid tumor cells

“…Our data show that miR-372 is aberrantly expressed in a half of PAds and in the majority of both atypical PAds and PCas, where it is also present at significantly higher levels than in PAds. Therefore, aggressive behavior in parathyroid tumors appears to be associated with enriched expression of the embryonic miR-372, similar to what was reported for glioma, colorectal and oral cancers (Yamashita et al 2012, Chen et al 2015, Tu et al 2015. In this context, it is noteworthy that PAts showed a miR-372 expression pattern close to that detected in PCas.…”

“…In parathyroid tumor cells, miR-372 represses the cell cycle genes CDKN1A/p21, LATS2 and cyclin D1 thereby explaining the slow proliferating nature of this neoplasm, and potentially protects parathyroid cells from apoptotic stimuli, such as exposure to chemotherapeutics. miR-372 has been shown to play a substantial role in several human cancers, where it is either upregulated (Voorhoeve et al 2006, Cho et al 2009, Yamashita et al 2012, Li et al 2013, Chen et al 2015, Tu et al 2015, Liu et al 2016 or downregulated (Tian et al 2011, Huang et al 2015, Liu et al 2016. Our data show that miR-372 is aberrantly expressed in a half of PAds and in the majority of both atypical PAds and PCas, where it is also present at significantly higher levels than in PAds.…”

Differential expression analysis at the individual level reveals a lncRNA prognostic signature for lung adenocarcinoma

“…By integrating the lncRNA-miRNA interactions and miRNA-target interactions in databases of miRanda [36], miRTarBase [37], miRcode [38] and TargetScan [39], we found C1orf132 was significantly competitively binding miRNAs with RBL2 ( P  = 2.38 × 10 −12 , hypergeometric test) and CCND3 ( P  = 9.82 × 10 −5 , hypergeometric test) (Additional file 6: Table S12). Some miRNAs, such as hsa-miR-93 [40], hsa-miR-372 [41], hsa-miR-424 [42], have been reported the important roles in the progression of LUAD. Thus, we inferred that the down-regulation of C1orf132 might release the miRNAs that targeted RBL2 and CCND3 and further promote the tumor progression, which warrant further in-depth experimental research.…”

MiR‐372‐3p promotes cell growth and metastasis by targeting FGF9 in lung squamous cell carcinoma

“…Although miR‐372‐3p has been found to regulate cancer development by suppressing various genes in various tumors , it was worth mentioning that the FGF9 was chosen as the candidate target gene using bioinformatics analysis. In this study, we found that miR‐372‐3p depressed the expression of FGF9 directly.…”