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miR-372 regulates glioma cell proliferation and invasion by directly targeting PHLPP2
Xin Chen1, Bin Hao, Guosheng Han
1Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
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.
Insights
MicroRNA-372 (miR-372) acts as an oncogene in glioma by promoting cancer cell growth and spread. Inhibiting miR-372 suppresses tumor development by targeting PHLPP2 and affecting the PI3K/Akt pathway.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are implicated in cancer development and progression.
- The specific role of microRNA-372 (miR-372) in glioma pathogenesis is not well understood.
Purpose of the Study:
- To investigate the function and mechanism of miR-372 in glioma.
- To determine if miR-372 acts as an oncogene or tumor suppressor in glioma.
Main Methods:
- Quantitative real-time PCR to measure miR-372 expression in glioma tissues and cell lines.
- Cell proliferation, invasion, apoptosis, and cell cycle assays after miR-372 knockdown.
- Xenograft mouse models to assess tumor growth inhibition.
- Luciferase reporter assays to confirm direct targeting of PHLPP2 by miR-372.
- Western blotting to analyze protein expression, including PI3K/Akt pathway components.
Main Results:
- miR-372 was significantly upregulated in glioma cell lines and tissues.
- Downregulation of miR-372 inhibited glioma cell proliferation and invasion, induced apoptosis, and caused G1/S cell cycle arrest.
- miR-372 directly targets the 3'-untranslated region of PHLPP2, and its expression is inversely correlated with PHLPP2 levels in glioma.
- Knockdown of PHLPP2 reversed the inhibitory effects of miR-372 inhibition.
- miR-372 knockdown suppressed the phosphorylation of Akt, mTOR, and P70S6K in the PI3K/Akt pathway.
Conclusions:
- miR-372 functions as an oncogenic miRNA in glioma by targeting PHLPP2.
- miR-372 promotes glioma progression through the PI3K/Akt signaling pathway.
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