Long noncoding RNA AK023096 interacts with hnRNP-K and contributes to the maintenance of self-renewal in bladder cancer stem-like cells

Fengjin Zhao; Shizhong Qin; Li Huang; Langjin Ding; Xingyuan Shi; Guangzheng Zhong

doi:10.1016/j.yexcr.2021.112909

Long noncoding RNA AK023096 interacts with hnRNP-K and contributes to the maintenance of self-renewal in bladder cancer stem-like cells

Exp Cell Res. 2021 Dec 15;409(2):112909. doi: 10.1016/j.yexcr.2021.112909. Epub 2021 Nov 4.

Authors

Fengjin Zhao¹, Shizhong Qin², Li Huang³, Langjin Ding⁴, Xingyuan Shi⁵, Guangzheng Zhong⁶

Affiliations

¹ Guangzhou Key Laboratory of Enhanced Recovery after Abdominal Surgery, Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, No.621, Gangwan Road, Guangzhou, Guangdong, 510799, China. Electronic address: zhfj621@163.com.
² Department of Urology, Liuzhou Maternity and Child Healthcare Hospital, No.621, Gangwan Road, Liuzhou, Guangxi, 545001, China. Electronic address: 976250600@qq.com.
³ Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107, Yanjiang Road, Guangzhou, Guangdong, 510120, China. Electronic address: huangli855@163.com.
⁴ Guangzhou Key Laboratory of Enhanced Recovery after Abdominal Surgery, Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, No.621, Gangwan Road, Guangzhou, Guangdong, 510799, China. Electronic address: 917691775@qq.com.
⁵ Guangzhou Key Laboratory of Enhanced Recovery after Abdominal Surgery, Department of Oncology Radiotherapy, The Fifth Affiliated Hospital of Guangzhou Medical University, No.621, Gangwan Road, Guangzhou, Guangdong, 510799, China. Electronic address: shixingyuansums@qq.com.
⁶ Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107, Yanjiang Road, Guangzhou, Guangdong, 510120, China. Electronic address: zhonggzh3@mail.sysu.edu.cn.

PMID: 34742742
DOI: 10.1016/j.yexcr.2021.112909

Abstract

LncRNA contribution to self-renewal of bladder cancer stem-like cells (CSLCs) remains largely unknown. We investigated the expression profile and biological function of lncRNAs in urothelial CSLCs by microarray analysis. Among these, lncRNA-AK023096 was identified as potentially playing a role in maintaining self-renewal of CSLCs. Knockdown of this transcript inhibited spheroid formation and tumor formation. We found that AK023096 mediates recruitment of hnRNP-K to SOX2 promoter and increases H3K4 trimethylation status on SOX2 promoter, leading to a robust change in SOX2 mRNA and protein levels. Moreover, AK023096 expression in primary tumors was found to be a powerful predictor of recurrence following transurethral resection in patients with nonmuscle-invasive bladder cancer, highlighting the critical role of lncRNA in the bladder cancer regulatory network.

Keywords: Bladder cancer; Cancer stem-like cells; SOX2; hnRNP-K; lncRNA.

Publication types

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

MeSH terms

Animals
Apoptosis
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism*
Cell Proliferation
Cell Self Renewal*
Gene Expression Regulation, Neoplastic
Heterogeneous-Nuclear Ribonucleoprotein K / genetics
Heterogeneous-Nuclear Ribonucleoprotein K / metabolism*
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplastic Stem Cells / metabolism
Neoplastic Stem Cells / pathology*
Prognosis
Promoter Regions, Genetic
RNA, Long Noncoding / genetics*
SOXB1 Transcription Factors / genetics
SOXB1 Transcription Factors / metabolism*
Survival Rate
Tumor Cells, Cultured
Urinary Bladder Neoplasms / genetics
Urinary Bladder Neoplasms / metabolism
Urinary Bladder Neoplasms / pathology*
Xenograft Model Antitumor Assays

Substances

Biomarkers, Tumor
Heterogeneous-Nuclear Ribonucleoprotein K
RNA, Long Noncoding
SOXB1 Transcription Factors
HNRNPK protein, human