Identification of miRNA signature associated with BMP2 and chemosensitivity of TMZ in glioblastoma stem-like cells

Xiaoyu Guo; Ziguo Luo; Tong Xia; Lanxiang Wu; Yanshu Shi; Ying Li

doi:10.1016/j.gendis.2019.09.002

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Identification of miRNA signature associated with BMP2 and chemosensitivity of TMZ in glioblastoma stem-like cells

Full-length article | 更新时间：2022-06-24

- Identification of miRNA signature associated with BMP2 and chemosensitivity of TMZ in glioblastoma stem-like cells
- Identification of miRNA signature associated with BMP2 and chemosensitivity of TMZ in glioblastoma stem-like cells
- Genes & Diseases 2020年7卷第3期
- 作者机构：
  
  1. Life Science Institute, Chongqing Medical University,Chongqing,China
  2. Department of Radiology, Southwest Hospital, Third Military Medical University,Chongqing,China
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2019.09.002
  中图分类号：
- 纸质出版日期：2020，
  
  网络出版日期：2020-9-1，
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Xiaoyu Guo, Ziguo Luo, Tong Xia, 等. Identification of miRNA signature associated with BMP2 and chemosensitivity of TMZ in glioblastoma stem-like cells[J]. Genes & Diseases, 2020,7(3).

Xiaoyu Guo, Ziguo Luo, Tong Xia, et al. Identification of miRNA signature associated with BMP2 and chemosensitivity of TMZ in glioblastoma stem-like cells[J]. Genes & Diseases, 2020,7(3).
Xiaoyu Guo, Ziguo Luo, Tong Xia, 等. Identification of miRNA signature associated with BMP2 and chemosensitivity of TMZ in glioblastoma stem-like cells[J]. Genes & Diseases, 2020,7(3). DOI： 10.1016/j.gendis.2019.09.002.

Xiaoyu Guo, Ziguo Luo, Tong Xia, et al. Identification of miRNA signature associated with BMP2 and chemosensitivity of TMZ in glioblastoma stem-like cells[J]. Genes & Diseases, 2020,7(3). DOI： 10.1016/j.gendis.2019.09.002.

摘要

Abstract

Glioblastoma multiform (GBM) is the most lethal intracranial tumor in adults. Glioblastoma stem-like cells (GSCs) are responsible for tumorigenesis and chemotherapy resistance. BMPs are known to increase temozolomide (TMZ) response in GSCs

however

the intracellular molecular mechanism remains largely unknown. In this study

we built a GSC cell model called U87S

and performed RNA sequencing to identify differentially expressed (DE) miRNA profiles in U87S cells treated with BMP2

TMZ or combined BMP2 and TMZ respectively. Bioinformatics analysis revealed that most DE miRNAs were involved in the cancer pathways

suggesting their crucial roles in gliomagenesis. Eight miRNAs from RNA-seq were validated. Four out of these miRNAs (

has-miR-199a-3p

hsa-miR-374b-5p

hsa-miR-320d

and

hsa-miR-339-5p

) were found significantly up-regulated in GBM tumor tissues. One of them

hsa-miR-199a-3p

was significantly correlated with the survival of GBM patients

and differentially expressed in U87S cells. Expression of

hsa-miR-199a-3p

was up-regulated by BMP. Overexpression of

hsa-miR-199a-3p

in U87S cells inhibited cell viability and enhanced the cytotoxicity of TMZ. And activation of BMP boosted the effect of

hsa-miR-199a-3p

on cell viability and TMZ-mediated cytotoxicity. Besides

expressions of five predicted targets of

hsa-miR-199a-3p

were evaluated. Four of them were differentially expressed in GBM tumors. And one of them

SLC22A18

was associated with the survival of GBM patients. In the end

hsa-miR-199a-3p

-mediated ceRNA network was constructed for the convenience of future study. Together

our data provided DE miRNA expression profiles associated with BMP2 and TMZ in GSCs

which might lead to finding out miRNA-based target therapies that specially target GSCs.

关键词

Keywords

BMP2Cancer stem cellCeRNAGliobalstomaRNA-seqTMZ

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