Long Noncoding RNA NONHSAT079852.2 Contributes to GBM Recurrence by Functioning as a ceRNA for has-mir-10401-3p to Facilitate HSPA1A Upregulation
| Autor: | Lili Zhao, Chao Chen, Yang Jiao, Jiajie Zhang, Min Chao, Haiyan Cao, Liang Wang, Xiaoni Fu, Qian Zhao, Yaqin Hu, Huijuan Wang, Ningning Zhao |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research RNA-sequencing lncRNAs Biology recurrent glioblastoma multiforme Pathogenesis 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Glioma medicine Gene RC254-282 HSPA1A Original Research Gene knockdown Competing endogenous RNA Neoplasms. Tumors. Oncology. Including cancer and carcinogens ceRNA medicine.disease Long non-coding RNA 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research |
| Zdroj: | Frontiers in Oncology Frontiers in Oncology, Vol 11 (2021) |
| ISSN: | 2234-943X |
| Popis: | Glioblastoma multiforme (GBM) is the most common brain malignancy and major cause of high mortality in patients with GBM, and its high recurrence rate is its most prominent feature. However, the pathobiological mechanisms involved in recurrent GBM remain largely unknown. Here, whole-transcriptome sequencing (RNA-sequencing, RNA-Seq) was used in characterizing the expression profile of recurrent GBM, and the aim was to identify crucial biomarkers that contribute to GBM relapse. Differentially expressed RNAs in three recurrent GBM tissues compared with three primary GBM tissues were identified through RNA-Seq. The function and mechanism of a candidate long noncoding RNA (lncRNA) in the progression and recurrence of GBM were elucidated by performing comprehensive bioinformatics analyses, such as functional enrichment analysis, protein–protein interaction prediction, and lncRNA–miRNA–mRNA regulatory network construction, and a series of in vitro assays. As the most significantly upregulated gene identified in recurrent GBM, HSPA1A is mainly related to antigen presentation and the MAPK signaling pathway, as indicated by functional enrichment analysis. HSPA1A was predicted as the target gene of the lncRNA NONHSAT079852.2. qRT-PCR revealed that NONHSAT079852.2 was significantly elevated in recurrent GBM relative to that in primary GBM, and high NONHSAT079852.2 expression was associated with the poor overall survival rates of patients with GBM. The knockdown of NONHSAT079852.2 successfully induced tumor cell apoptosis, inhibited the proliferation, migration, invasion and the expression level of HSPA1A in glioma cells. NONHSAT079852.2 was identified to be a sponge for hsa-miR-10401-3p through luciferase reporter assay. Moreover, HSPA1A was targeted and regulated by hsa-miR-10401-3p. Collectively, the results suggested that NONHSAT079852.2 acts as a sponge of hsa-mir-10401-3p and thereby enhances HSPA1A expression, promotes tumor cell proliferation and invasion, and leads to the progression and recurrence of GBM. This study will provide new insight into the regulatory mechanisms of NONHSAT079852.2-mediated competing endogenous RNA in the pathogenesis of recurrent GBM and evidence of the potential of lncRNAs as diagnostic biomarkers or potential therapeutic targets. |
| Databáze: | OpenAIRE |
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