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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
MicroRNA-423-3p promotes glioma growth by targeting PANX2
1Department of Otolaryngology, Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Abstract:
Previously, a number of microRNAs (miRs) have been identified to participate in the development and progression of glioma via the regulation of their target genes. However, the molecular mechanisms underlying the effect of miR-423-3p in glioma growth remain unclear. In the present study, the reverse transcription-quantitative polymerase chain reaction and western blotting were used to assess the mRNA and protein expression levels of miR-423-3p, respectively. An MTT assay and flow cytometry were performed to determine cell proliferation and apoptosis, respectively. A luciferase reporter gene assay was performed to determine the target association between pannexin 2 (PANX2) and miR-423-3p. It was revealed that miR-423-3p was significantly upregulated in glioma tissues compared with normal brain tissues, and the increased expression of miR-423-3p was significantly associated with an advanced grade as well as a poorer prognosis of patients with glioma. Inhibition of miR-423-3p using an miR-423-3p inhibitor resulted in the decreased proliferation of glioma U251 and U87MG Uppsala cells, and the induction of apoptosis. PANX2 was identified as a novel target gene of miR-423-3p, and the expression of PANX2 was revealed to be increased in U251 and U87MG Uppsala cells when miR-423-3p was inhibited. Knockdown of PANX2 attenuated the effects of miR-423-3p inhibition on glioma cell proliferation and apoptosis. Furthermore, PANX2 was significantly downregulated in glioma tissues compared with normal brain tissues, and its levels were markedly lower in World Health Organization (WHO) stage III-IV gliomas compared with WHO stage I-II gliomas. Additionally, the expression levels of PANX2 were identified to be inversely correlated with miR-423-3p expression levels in glioma tissues. Consequently, targeting miR-423-3p may inhibit glioma growth via the upregulation of PANX2.
Insights
MicroRNA-423-3p promotes glioma growth by downregulating PANX2. Inhibiting miR-423-3p or increasing PANX2 levels may offer new therapeutic strategies for glioma patients.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRs) play a crucial role in glioma development and progression by regulating target genes.
- The specific molecular mechanisms of miR-423-3p in glioma remain largely uncharacterized.
Purpose of the Study:
- To elucidate the role of miR-423-3p in glioma growth and identify its molecular targets.
- To investigate the potential of targeting miR-423-3p as a therapeutic strategy for glioma.
Main Methods:
- Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting to measure miR-423-3p and PANX2 expression.
- MTT assay and flow cytometry to assess glioma cell proliferation and apoptosis.
- Luciferase reporter gene assay to confirm the direct targeting of PANX2 by miR-423-3p.
Main Results:
- miR-423-3p was significantly upregulated in glioma tissues and correlated with advanced grade and poor prognosis.
- Inhibition of miR-423-3p reduced glioma cell proliferation and induced apoptosis.
- PANX2 was identified as a direct target of miR-423-3p, with its expression inversely correlated with miR-423-3p in glioma tissues.
- Downregulation of PANX2 was observed in glioma tissues, particularly in higher WHO stages.
Conclusions:
- miR-423-3p promotes glioma progression by suppressing PANX2 expression.
- Targeting miR-423-3p to upregulate PANX2 presents a potential therapeutic avenue for inhibiting glioma growth.
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