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

Abstract

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.

STAT3 Inhibitors: A Novel Insight for Anticancer Therapy of Pancreatic Cancer

“…Similarly, lncRNAs can also regulate STAT3 expression and activation directly or indirectly through a variety of mechanisms, and this regulation is mostly achieved through endosomal competitive RNAs. For example, LINC00115 and CASC9 can further regulate STAT3 function by regulating downstream miRNA in cancer disease [ 39 , 40 ]. Moreover, activation of STAT3 can be induced by phosphorylation of some receptor tyrosine kinases themselves.…”

Propofol suppresses proliferation, migration, invasion, and tumor growth of liver cancer cells via suppressing cancer susceptibility candidate 9/phosphatase and tensin homolog/AKT serine/threonine kinase/mechanistic target of rapamycin kinase axis

“…Virtually, CASC9 has been reported to interact with EZH2 and subsequently regulate gene expression at epigenetic levels. [28][29][30][31] RIP assay was used to evaluate the interaction between CASC9 and EZH2. We found that CASC9 was successfully pulled down by EZH2 compared with IgG control, indicating that CASC9 could bind to EZH2 directly (Figure 5(c)).…”

Small in Size, but Large in Action: microRNAs as Potential Modulators of PTEN in Breast and Lung Cancers

“…IL-8 can reduce PTEN expression via phosphorylation to stimulate STAT3 signaling, resulting in enhanced cancer progression [ 161 ]. Furthermore, STAT3 can function as an upstream mediator of PTEN by activating lncRNA cancer susceptibility candidate 9 (CASC9) to diminish PTEN expression, resulting in bladder cancer progression [ 162 ]. On the other hand, miRNAs such as miRNA-551b-3p can induce STAT3 signaling in enhancing the growth and metastasis of cancer cells [ 163 ].…”