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 , signal transducer and activator of transcription 3 , phosphatase and tensin homolog , enhancer of zeste homolog 2