Hypoxia‐inducible lncRNA MIR210HG interacting with OCT1 is involved in glioblastoma multiforme malignancy

Abstract

An insufficient oxygen supply within the intratumoral environment, also known as hypoxia, induces glioblastoma multiforme (GBM) invasion, stemness, and temozolomide (TMZ) drug resistance. Long noncoding (lnc)RNAs have been reported to be involved in hypoxia and GBM progression. However, their roles in hypoxic GBM malignancy are still unclear. We investigated the mechanisms of hypoxia-mediated lncRNAs in regulating GBM processes. Using The Cancer Genome Atlas (TCGA) and data mining, hypoxia-correlated lncRNAs were identified. A hypoxia-upregulated lncRNA, MIR210HG, locating in nuclear regions, predicted poor prognoses of patients and modulated hypoxia-promoted glioma stemness, TMZ resistance, and invasion.Depletion of hypoxic MIR210HG suppressed GBM and patient-derived cell growth and increased TMZ sensitivity in vitro and vivo. Using RNA sequencing and gene set enrichment analysis (GSEA), MIR210HG-upregulated genes significantly belonged to the targets of octamer transcription factor 1 (OCT1) transcription factor. The direct interaction between OCT1 and MIR210HG was also validated. Two well-established worse prognostic factors of GBM, insulin-like growth factor-binding protein 2 (IGFBP2) and fibroblast growth factor receptor 1 (FGFR1), were identified as downstream targets of OCT1 through MIR210HG mediation in hypoxia. Consequently, the lncRNA MIR210HG is upregulated by hypoxia and interacts with OCT1 for modulating hypoxic GBM, leading to poor prognoses. These findings might provide a better understanding in functions of hypoxia/MIR210HG signaling for regulating GBM malignancy.

A novel hypoxia-driven gene signature that can predict the prognosis and drug resistance of gliomas

“…Previous studies indicated that hypoxia can regulated a series oncogenes (Liu et al, 2020) or non-coding RNAs (Ho et al, 2022) to induce TMZ-resistance of glioma. In the current study, we demonstrated that SHOX2 was increased TMZresistance glioma cells, while hypoxia can induced the elevation of SHOX2 in glioma cells.…”

M7G-related LncRNAs: A comprehensive analysis of the prognosis and immunity in glioma

“…In addition, there are pieces of evidence that lncRNAs play an essential part in cancer ( Ho et al, 2022 ; Liang et al, 2022 ; Zhang et al, 2022 ). SNAI3-AS1 , an m 7 G prognosis-associated lncRNA, is an important tumor modifier in hepatocellular carcinoma tumor progression ( Li et al, 2020 ).…”

Progress in the studies on the molecular mechanisms associated with multidrug resistance in cancers

“…It is recently reported that, downregulation of lncRNA plasmacytoma variant translocation 1 (PVT1) increased sensitivity of BC sells to doxorubicin (ADM), suppressed ADM-resistant BC cell proliferation and invasion, and promoted apoptosis, while PVT1 overexpression promoted ADM-sensitive BC cell growth and their resistance to ADM 97 , and the potential mechanisms that mediate the alteration could be related with the elevated MDM2 expression and AURKB-mediated p53 ubiquitination 97 . Studies showed that some of the lncRNAs could interact with transcription factors, for example, lncRNA MIR210HG, locating in nuclear regions, could interact with octamer transcription factor 1 (OCT1) 111 .…”