STAT3-Induced Upregulation of lncRNA CASC9 Promotes the Progression of Bladder Cancer by Interacting with EZH2 and Affecting the Expression of PTEN

Onco Targets Ther. 2020 Sep 16;13:9147-9157. doi: 10.2147/OTT.S248006. eCollection 2020.


Objective: Long non-coding RNA (lncRNA) cancer susceptibility candidate 9 (CASC9) has been reported to play a vital role in tumorigenesis. This study explored the biological role of CASC9 and its regulation mechanism in bladder cancer (BC).

Methods: Gene expression was evaluated using quantitative reverse transcription polymerase chain reaction and Western blot. The functional role of CASC9 in BC was studied using Cell Counting Kit-8, colony formation assay, scratch wound healing assay, transwell invasion assay, and xenograft tumor assay. In addition, the mechanism of CASC9 function in BC was determined using RNA immunoprecipitation assay and chromatin immunoprecipitation assay.

Results: CASC9 was upregulated in BC tissues and cell lines, and correlated with the staging and metastasis in BC. Knockdown of CASC9 inhibited the proliferation, migration, and invasion of BC cells. Similarly, silencing of CASC9 inhibited tumor growth in vivo. Signal transducer and activator of transcription 3 (STAT3) was upregulated in BC tissues and cell lines, and positively correlated with CASC9 in BC tissues. Moreover, CASC9 was shown to be regulated by STAT3 in BC cells. Furthermore, CASC9 regulated phosphatase and tensin homolog (PTEN) expression by interacting with enhancer of zeste homolog 2 (EZH2). More significantly, CASC9 silencing-mediated inhibition of BC progression was partly reversed by EZH2 overexpression or PTEN inhibition.

Conclusion: Upregulation of CASC9 induced by STAT3 promoted the progression of BC by interacting with EZH2 and affecting the expression of PTEN, representing a novel regulatory mechanism for BC progression.

Keywords: bladder cancer; cancer susceptibility candidate 9; enhancer of zeste homolog 2; phosphatase and tensin homolog; signal transducer and activator of transcription 3.