LINC01152 upregulates MAML2 expression to modulate the progression of glioblastoma multiforme via Notch signaling pathway

Jianheng Wu,Nannan Wang,Guangyuan Jiang,Hui Zhan,Fuyong Li,Ying Yang

doi:10.1038/s41419-020-03163-9

Abstract

Glioblastoma multiforme (GBM) brings serious physical and psychological pain to GBM patients, whose survival rate remains not optimistic. Long noncoding RNAs (lncRNAs) have been reported to participate in the progression of many cancers, including GBM. However, the mechanism and function of long intergenic non-protein coding RNA 1152 (LINC01152) in GBM are still unclear. In our study, we aimed to explore the function and mechanism of LINC01152 in GBM. Then qRT-PCR analysis was implemented to search the expression of RNAs in GBM tissues and cells. Functional assays such as EdU assay, colony formation assay, TUNEL assay and flow cytometry analysis were conducted to estimate GBM cell proliferation and apoptosis. RNA pull down assay, luciferase reporter assay, RIP and ChIP assays were implemented to search the binding between molecules. As a result, we discovered that LINC01152 was upregulated in GBM tissues and cells. LINC01152 and mastermind like transcriptional coactivator 2 (MAML2) could both play the oncogenic part in GBM. Moreover, LINC01152 positively regulated MAML2 in GBM by sponging miR-466 and recruiting SRSF1. In turn, RBPJ/MAML2 transcription complex was found to activate the transcription of LINC01152 in GBM cells. In conclusion, LINC01152 could upregulate the expression of MAML2 to promote tumorigenesis in GBM via Notch signaling pathway.

Highlights

Glioblastoma multiforme (GBM) is the most deadly brain tumor and at least 4 in 100,000 people come down with GBM every year[1]
LncRNA ZFAS1 has been identified as a regulator of colorectal cancer cell migration and invasion and its overexpression connects to shorter overall survival of colorectal cancer patients[11]
LINC01152 expression was identified to be highly expressed in GBM and brain lower grade glioma (LGG) through GEPIA database (Fig. 1A) and LINC01152 was further unveiled to be upregulated in GBM and LGG tissues (Fig. 1B and Fig. S1A) according to GEPIA database

Summary

Introduction

Glioblastoma multiforme (GBM) is the most deadly brain tumor and at least 4 in 100,000 people come down with GBM every year[1]. Even though much improvements have been made in surgery treatment, radiotherapy, and chemotherapy, most of GBM patients can live longer than 1 year after diagnosis[3,4]. LncRNAs have been verified to modulate the growth, migration and invasion of cancer cells, functioning as tumor promoters or suppressers in cancer[9,10]. LncRNA ZFAS1 has been identified as a regulator of colorectal cancer cell migration and invasion and its overexpression connects to shorter overall survival of colorectal cancer patients[11]. LncRNA ENST457720 can function as an Official journal of the Cell Death Differentiation Association

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