Identification of stemness index-related long noncoding RNA SNHG12 in human bladder cancer based on WGCNA

Bin Zhang; Yang He; Gui Ma; Lili Zhang; Peng Qi; Dali Han; Zhongjin Yue; Panfeng Shang

doi:10.1016/j.mcp.2022.101867

Identification of stemness index-related long noncoding RNA SNHG12 in human bladder cancer based on WGCNA

Mol Cell Probes. 2022 Dec:66:101867. doi: 10.1016/j.mcp.2022.101867. Epub 2022 Sep 29.

Authors

Bin Zhang¹, Yang He¹, Gui Ma¹, Lili Zhang¹, Peng Qi¹, Dali Han¹, Zhongjin Yue¹, Panfeng Shang²

Affiliations

¹ Department of Urology, Institute of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, Lanzhou University Second Hospital, No. 82 Cui Ying Gate, Cheng Guan District, Lanzhou, 730030, Gansu, China.
² Department of Urology, Institute of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, Lanzhou University Second Hospital, No. 82 Cui Ying Gate, Cheng Guan District, Lanzhou, 730030, Gansu, China. Electronic address: shangpf@lzu.edu.cn.

PMID: 36183925
DOI: 10.1016/j.mcp.2022.101867

Abstract

Background: Cancer stem cells (CSCs) have an key role in the beginning, progression and treatment of bladder cancer. In the current study, our target was to identify CSCS-related genes in bladder cancer.

Methods: Bladder cancer (BLCA) transcriptome data were acquired from The Cancer Genome Atlas (TCGA) database. WGCNA was used to screen genes connected with the mRNA expression-based stemness index (mRNAsi).Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to analyze the biological function of mRNAsi-related genes. Univariate Cox regression and LASSO Cox regression algorithms were applied to build a risk score model. Additionally, a ceRNA regulatory netwok based on key mRNAsi-related genes was established via TargetScan, miRDB, miRTarBas and miRcode database,and lncRNA SNHG12 was selected for further in vitro and invivo functional assays.

Results: Between BLCA and normal samples were identified 1560 differentially expressed genes (DEGs).845 DEGs were most significantly associated with mRNAsi according to WGCNA analysis, which were mainly enriched in GO terms and KEGG pathways related to cell proliferation. Univariate Cox regression and LASSO Cox regression algorithms screened 25 mRNAsi-related genes to construct the risk score model with the significant ability to estimate prognosis of BLCA patients. A ceRNA network, including 8 lncRNA, 11 miRNA and 9 mRNAsi-related mRNA, was constructed.We found that lncRNAs ADAMTS9-AS1 and SNHG12 were observably related to the survival of BLCA patients. To verify this finding, we selected SNHG12 for further study. RT-PCR experiments revealed that SNHG12 was high expression in both bladder cancer tissues and cells.SNHG12 promoted proliferation, invasion, migration, apoptosis and stemness of bladder cancer cells in vitro and tumour proliferation in vivo.

Conclusion: Our study identified 25 biomarkers associated with stemness indices in BLCA and established a ceRNA network based on key mRNAsi-related genes.SNHG12 promoted BLCA proliferation, invasion, migration, apoptosis and stemness in vitro. It was also showed that SNHG12 promoted tumour growth.

Keywords: Bladder cancer; Prognosis; Stemness; WGCNA; lncRNA; mRNAsi.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Gene Expression Regulation, Neoplastic
Gene Ontology
Gene Regulatory Networks
Humans
RNA, Long Noncoding* / genetics
RNA, Messenger / genetics
Urinary Bladder Neoplasms* / genetics

Substances

RNA, Long Noncoding
RNA, Messenger
SNHG12 long non-coding RNA, human