Abstract
ObjectiveAccumulating evidence has highlighted the roles of long noncoding RNAs (lncRNAs) as competing endogenous RNAs (ceRNAs) of microRNAs (miRNAs) through their binding sites in the progression of glioma. Hereby, we aim to explore the role of LINC00883 as a regulator of miR-136 and its target, NIMA-related kinase 1 (NEK1), thus, its involvement in the drug resistance of glioma cells.Methods and ResultsMechanistic investigations by dual-luciferase reporter, RNA pull-down, and RNA-binding protein immunoprecipitation (RIP) assays indicated that LINC00883 bound to miR-136, thereby blocking miR-136-induced downregulation of NEK1. Through gain-of-function experiments in U251 cells that presented a high drug resistance, we found that ectopic expression of LINC00883 resulted in increased MRP (encoding multidrug resistance-associated protein), limited cell apoptosis, and increased proliferation. Expectedly, depleting LINC00883 yielded tumor-suppressive and anti-chemoresistance effects on U251 cells by increasing miR-136 and inhibiting NEK1. Next, drug-resistant glioma cell line SOWZ1, drug-sensitive glioma cell line SOWZ2, and drug-resistant glioma cell line SOWZ2-BCNU (SOWZ2 cultured in BCNU) were applied to validate the roles of LINC00883 in the regulation of multidrug resistance. LINC00883 knockdown suppressed the viability of SWOZ1, SWOZ2, and SWOZ2-BCNU cells.ConclusionIn conclusion, LINC00883 knockdown reduces drug resistance in glioma. Hence, our study provides a future strategy to prevent drug resistance-induced therapeutic failure in glioma.
Highlights
Gliomas are heterogeneous tumors that originate from the glial cells and have been regarded as the most fatal form of brain cancer [1]
With “glioma” used as the key word, microarray data related to glioma (GSE15824 and GSE4290) and their annotated probe files were downloaded from the Gene Expression Omnibus (GEO) database, and the microarray data were obtained by Human Genome U133 Plus 2.0 Array (Affymetrix, Inc., CA, USA)
The above results indicated that LINC00883 may regulate NEK1 to participate in the occurrence and development of glioma through miR-136
Summary
Gliomas are heterogeneous tumors that originate from the glial cells and have been regarded as the most fatal form of brain cancer [1]. Glioma manifests itself as a primary tumor and has a high mortality due to the inefficacy of current treatment protocols, which include chemotherapy against which gliomas developed resistance [6]. Accumulating evidence has been presented by various investigations conducted into novel, more effective glioma therapy methods [3, 7]. A recent study has revealed that potential treatment regimens could be developed through the connection between the regulators of the cellular process (growth, differentiation, proliferation, and apoptosis) [5]. It is of great significance that investigations are opened into such markers that are implicated in key tumorigenic events in order to identify more effective glioma treatment methods
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