Abstract
ObjectivesLong non-coding RNAs (lncRNAs) are key regulators involved in the progression of glioma, and many functional lncRNAs are yet to be identified. This study aimed to explore the function of CHRM3-AS2, a rarely reported lncRNA, in glioma, as well as the underlying mechanisms involving miR-370-5p/KLF4.MethodsDifferentially expressed RNAs (DERs) were screened from two gene expression profiles of glioblastoma (GBM). Fluorescence in situ hybridisation was performed to determine the subcellular localisation of CHRM3-AS2. Cell viability, colony formation, apoptosis, migration, and invasion were evaluated using cell counting kit-8, colony counts, flow cytometry, wound healing, and Transwell assays, respectively. mRNA and protein expression of specific genes were measured using quantitative real-time polymerase chain reaction and western blotting, respectively. Dual luciferase reporter gene, RNA immunoprecipitation, and RNA pull-down assays were performed to identify the target relationships. A mouse xenograft model was established for in vivo validation.ResultsCHRM3-AS2 was screened as a prognosis-associated DER in GBM. CHRM3-AS2 expression was up-regulated in glioma cells, and CHRM3-AS2 was localised in the cytoplasm. Silencing of CHRM3-AS2 expression inhibited cell viability, colony formation, migration, and invasion and promoted apoptosis of U251 and SHG-44 cells. In addition, CHRM3-AS2 targeted miR-370-5p/KLF4 in glioma cells. The anti-tumour effect of CHRM3-AS2 silencing was weakened by miR-370-5p silencing or KLF4 overexpression. In vivo, silencing of CHRM3-AS2 expression inhibited tumour growth and Ki67 expression in mice. Overexpression of KLF4 also weakened the anti-tumour effect of CHRM3-AS2 silencing in mice.ConclusionsSilencing of CHRM3-AS2 expression inhibited the malignant progression of glioma by regulating miR-370-5p/KLF4 expression.
Highlights
Glioma is a prevalent type of primary intracranial carcinoma, accounting for 81% of malignant brain tumours [1]
This study aimed to explore the function of CHRM3-AS2, a rarely reported Long non-coding RNAs (lncRNAs), in glioma, as well as the underlying mechanisms involving miR-370-5p/KLF4
CHRM3-AS2 was screened as a prognosis-associated Differentially expressed RNAs (DERs) in GBM
Summary
Glioma is a prevalent type of primary intracranial carcinoma, accounting for 81% of malignant brain tumours [1]. Glioma can be classified into the following subtypes: astrocytoma, oligodendroglioma, oligoastrocytoma, ependymoma, glioblastoma (GBM), and mixed tumours [2]. Conventional therapeutic strategies, including surgical resection, chemotherapy, and radiotherapy, are still limited in improving the prognosis of patients with glioma [3]. Grade IV GBM, the most common and malignant form of glioma, is more likely to be accompanied with poor prognosis because GBM stem-like cells are resistant to conventional therapy and undergo recurrence [4]. For GBM patients receiving current standard treatments, the median overall survival is approximately 12–18 months [5]. Discovery of novel therapeutic targets for glioma is urgently needed
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