Therapy-resistant and -sensitive lncRNAs, SNHG1 and UBL7-AS1 promote glioblastoma cell proliferation.

Mei Cao,Chi Zhang,Huaqing Li,Juan Cui,Jian Zhao,Rong Ma,Qiang Tong

doi:10.1155/2022/2623599

Abstract

The current treatment options for glioblastoma (GBM) can result in median survival of 15-16 months only, suggesting the existence of therapy-resistant factors. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play an essential role in the development of various brain tumors, including GBM. This study aimed to identify therapy-resistant and therapy-sensitive GBM associated lncRNAs and their role in GBM. We conducted a genome-wide transcriptional survey to explore the lncRNA landscape in 195 GBM brain tissues. Cell proliferation was evaluated by CyQuant assay and Ki67 immunostaining. Expression of MAD2L1 and CCNB2 was analyzed by western blotting. We identified 51 lncRNAs aberrantly expressed in GBM specimens compared with either normal brain samples or epilepsy non-tumor brain samples. Among them, 27 lncRNAs were identified as therapy-resistant lncRNAs that remained dysregulated after both radiotherapy and chemoradiotherapy; while 21 lncRNAs were identified as therapy-sensitive lncRNAs whose expressions were reversed by both radiotherapy and chemoradiotherapy. We further investigated the potential functions of the therapy-resistant and therapy-sensitive lncRNAs and demonstrated their relevance to cell proliferation. We also found that the expressions of several lncRNAs, including SNHG1 and UBL7-AS1, were positively correlated with cell-cycle genes' expressions. Finally, we experimentally confirmed the function of a therapy-resistant lncRNA, SNHG1, and a therapy-sensitive lncRNA, UBL7-AS1, in promoting cell proliferation in GBM U138MG cells. Our in vitro results demonstrated that knockdown of SNHG1 and UBL7-AS1 showed an additive effect in reducing cell proliferation in U138MG cells.

Highlights

Glioblastoma (GBM) is the most aggressive type of brain cancer [1]
Identification of dysregulated Long non-coding RNAs (lncRNAs) in various human brain tumors compared with normal brain tissues
We found that the expressions of therapy-resistant lncRNA SNHG1 and therapysensitive lncRNA UBL7-AS1 were positively correlated with the expressions of cell-cycle genes MAD2L1 and CCNB2, respectively

Summary

Introduction

Glioblastoma (GBM) is the most aggressive type of brain cancer [1]. The current treatment options, such as surgery, radiation, and chemotherapy in combination, can result in median survival of 15-16 months only [2]. There is an urgent need to identify novel therapeutic targets for the treatment of GBM. Long non-coding RNAs (lncRNAs) have emerged as critical players in the pathogenesis and development of various cancers, including malignant brain tumors such as GBM [3]. Studies have demonstrated that lncRNAs CRNDE [4], H19 [5], NEAT1 [5], LINC00461 [6], and HOTAIR [7] play an essential role in regulating both cell proliferation and migration in GBM. Loss-offunction studies have demonstrated that inhibition of lncRNAs MIR22HG [8], SPRY4-IT1 [9]), XIST [10], CCAT2 [11], LUCAT1 [12], and AB073614 [13]) successfully reduced certain GBM features, including proliferation Loss-offunction studies have demonstrated that inhibition of lncRNAs MIR22HG [8], SPRY4-IT1 (H. [9]), XIST [10], CCAT2 [11], LUCAT1 [12], and AB073614 (J. [13]) successfully reduced certain GBM features, including proliferation

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