Long noncoding RNA AK023096 interacts with hnRNP-K and contributes to the maintenance of self-renewal in bladder cancer stem-like cells
- 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)
- Department of Urology, Liuzhou Maternity and Child Healthcare Hospital, No.621, Gangwan Road, Liuzhou, Guangxi, 545001 (China)
- Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107, Yanjiang Road, Guangzhou, Guangdong, 510120 (China)
- 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)
Highlights: • BCSLCs play a critical role for the high risk of recurrence and we identified that lncRNA-AK023096 was required for controls stemness of BCSLCs. • LncRNA-AK023096 recruits hnRNP-K and epigenetically upregulated SOX2 expression by modulating H3K4 trimethylation of SOX2 promoter. • Overexpression of lncRNA-AK023096 expression in the tumor tissue was significantly associated with high risk of recurrence following TUR-Bt. 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.
- OSTI ID:
- 23195281
- Journal Information:
- Experimental Cell Research, Vol. 409, Issue 2; Other Information: Copyright (c) 2021 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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