American Association for Cancer Research
10780432ccr181656-sup-202510_2_supp_5102416_pgqxw8.pdf (4.55 MB)

Supplementary Data from Long Noncoding RNA LBCS Inhibits Self-Renewal and Chemoresistance of Bladder Cancer Stem Cells through Epigenetic Silencing of SOX2

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journal contribution
posted on 2023-03-31, 20:27 authored by Xu Chen, Ruihui Xie, Peng Gu, Ming Huang, Jinli Han, Wen Dong, Weibin Xie, Bo Wang, Wang He, Guangzheng Zhong, Ziyue Chen, Jian Huang, Tianxin Lin

Supplementary Data


National Natural Science Foundation of China

National Natural Science Foundation of Guangdong

Science and Technology Program of Guangzhou

Science and Technology Planning Project of Guangdong Province

Fundamental Research Funds for the Central Universities



Chemoresistance and tumor relapse are the leading cause of deaths in bladder cancer patients. Bladder cancer stem cells (BCSCs) have been reported to contribute to these pathologic properties. However, the molecular mechanisms underlying their self-renewal and chemoresistance remain largely unknown. In the current study, a novel lncRNA termed Low expressed in Bladder Cancer Stem cells (lnc-LBCS) has been identified and explored in BCSCs. Firstly, we establish BCSCs model and explore the BCSCs-associated lncRNAs by transcriptome microarray. The expression and clinical features of lnc-LBCS are analyzed in three independent large-scale cohorts. The functional role and mechanism of lnc-LBCS are further investigated by gain- and loss-of-function assays in vitro and in vivo. Lnc-LBCS is significantly downregulated in BCSCs and cancer tissues, and correlates with tumor grade, chemotherapy response, and prognosis. Moreover, lnc-LBCS markedly inhibits self-renewal, chemoresistance, and tumor initiation of BCSCs both in vitro and in vivo. Mechanistically, lnc-LBCS directly binds to heterogeneous nuclear ribonucleoprotein K (hnRNPK) and enhancer of zeste homolog 2 (EZH2), and serves as a scaffold to induce the formation of this complex to repress SRY-box 2 (SOX2) transcription via mediating histone H3 lysine 27 tri-methylation. SOX2 is essential for self-renewal and chemoresistance of BCSCs, and correlates with the clinical severity and prognosis of bladder cancer patients. As a novel regulator, lnc-LBCS plays an important tumor-suppressor role in BCSCs’ self-renewal and chemoresistance, contributing to weak tumorigenesis and enhanced chemosensitivity. The lnc-LBCS–hnRNPK–EZH2–SOX2 regulatory axis may represent a therapeutic target for clinical intervention in chemoresistant bladder cancer.