MicroRNA-142-3p is involved in regulation of <em>MGMT</em> expression in glioblastoma cells

Abstract

BackgroundGlioblastoma multiforme (GBM) is the most malignant brain tumor, and there is no effective treatment strategy. Patients with GBM have a median overall survival of only 14.6 months. Current treatment consists of safe and maximal surgical excision, followed by concurrent chemoradiotherapy and maintenance chemotherapy. There are several obstacles that hinder the effectiveness of this aggressive treatment. Temozolomide (TMZ) is an oral alkylating drug that acts through alkylating the O6 position of guanine in DNA that leads to cell death. However, the expression and enzymatic activity of the DNA repair protein MGMT limits the therapeutic benefit from treatment with TMZ. MGMT reduces the efficacy of alkylating drugs by removing the methyl or alkyl group from damaged O6-methylguanine. Expression levels of MGMT play an important role in the outcome of GBM patients. miRNAs are a group of small regulatory RNAs that control target gene expression by binding to mRNAs. miR-142-3p has been found to be an important factor in the development and maintenance of the oncogenic state.ResultsIn this study, we sought to investigate whether miR-142-3p can regulate MGMT gene expression in GBM cells. Here, we show that miR-142-3p downregulates MGMT expression through binding to the 3′-UTR of MGMT mRNA, thus affecting protein translation. Responsiveness to TMZ was significantly enhanced after transfection with miR-142-3p. Overexpression of miR-142-3p also sensitized GBM cells to alkylating drugs.ConclusionAbove all, our findings demonstrate that miR-142-3p plays a critical role in regulating MGMT expression, has great potential for future clinical applications, and acts as a new diagnostic marker for this intractable disease.

miR-142-3p Suppresses Cell Growth by Targeting CDK4 in Colorectal Cancer

“…Most recent, miR-142-3p has been reported to be associated with several types of cancer. MiR-142-3p was significantly upregulated in renal cell carcinoma and miR-142-3p inhibitor could significantly suppressed cell migration and proliferation, and promoted cell apoptosis in 786-O and ACHN cells [30]; miR-142-3p was down-regulated in both cancer cell lines and cancer specimens and miR-142-3p overexpression suppressed proliferation by leading cell cycle arrest in G2/M [31]; miR-142-3p was downregulated in hepatocellular carcinoma (HCC) tissues and the overexpression of miR-142-3p inhibited aerobic glycolysis and thus proliferation of HCC cells by targeting lactate dehydrogenase A (LDHA) [32]; miR-142-3p was significantly lower in ovarian cancer tissues and cell lines and Ectopic expression of miR-142-3p significantly inhibited the proliferation of ovarian cancer cells by targeting sirtuin 1 (SIRT1) and increased the sensitivity of SKOV3/DDP cells to cisplatin [33]; miR-142-3p was markedly downregulated in gastric cancer tissues and could inhibit the proliferation, invasion and migration of gastric cancer cells [34]; miR-142-3p inhibited proliferation and invasion in HeLa and SiHa cells by targeting frizzled 7 receptor [FZD7] [35]; miR-142-3p miR-142-3p downregulated MGMT expression and also sensitizedGlioblastoma multiforme [GBM] cells to alkylating drugs [36]; miR-142-3p overexpression increased PI3K, Akt, and mTOR phosphorylation by targeting High mobility group box-1 [HMGB1] in NSCLS cells [37]. According to CRC, three studies have suggested that miR-142-3p is involved in CRC development.…”

The Role of miRNA for the Treatment of MGMT Unmethylated Glioblastoma Multiforme

“…Lee et al determined an inverse correlation between MGMT and miR-142-3p expression levels in GBM cell lines: high MGMT expressing cell lines show low levels of miR-142-3p and low MGMT expressing cell lines show high levels of miR-142-3p [110]. In miR-142-3p overexpression experiments, no change in MGMT mRNA expression was observed, but a reduction in MGMT protein expression.…”

miR-142-3p as a novel biomarker for predicting poor prognosis in renal cell carcinoma patients after surgery

“…miR-142-3p is a promising miRNA that has been proved to be involved with several malignancies. 13–17 Moreover, a previous study has verified the correlation between miR-142-3p and prognosis of cervical cancer, revealing its potential to be a prognosis biomarker. 18 In order to explore the clinical significance of miR-142-3p, more investigation is necessary.…”