Long noncoding RNA XIST participates in bladder cancer by downregulating p53 via binding to TET1
Bo Hu1, Guowei Shi1, Qian Li2
1Department of Urology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.
Abstract:
Long noncoding RNAs (lncRNAs) have been reported to take part in intracellular RNA regulatory networks and play important roles in a lot of pathological processes. Currently, lncRNA X-inactive specific transcript (XIST) has been proved to regulate cell migration, proliferation, and apoptosis in a series of cancers. In this study, we explored whether XIST can affect cell proliferation, migration, and apoptosis in bladder cancer. The influences of XIST on the cell proliferation, cell cycle, and apoptosis were detected in bladder cancer cells. The effect of XIST on the migration of bladder cancer cells was examined by cell migration assay. Through RNA immunoprecipitation and chromatin immunoprecipitation assays, the binding relationship between XIST and TET1 and the regulatory mechanism of TET1 on p53 were examined. Western blot was performed to detect p53 after knockdown or overexpression of XIST. We found that knockdown of XIST suppressed cell migration and proliferation in vitro. Mechanistically, we confirmed that lncRNA XIST participates in bladder cancer by downregulating p53 via binding to TET1. In conclusion, our research revealed the potential role of XIST-TET1-p53 regulatory network in bladder cancer.
Insights
Long noncoding RNA XIST (XIST) knockdown suppresses bladder cancer cell migration and proliferation. XIST downregulates p53 by binding to TET1, revealing a novel XIST-TET1-p53 regulatory network in bladder cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long noncoding RNAs (lncRNAs) are implicated in cellular regulatory networks and disease pathology.
- The lncRNA X-inactive specific transcript (XIST) is known to influence cell migration, proliferation, and apoptosis in various cancers.
Purpose of the Study:
- To investigate the role of XIST in bladder cancer.
- To determine the effects of XIST on bladder cancer cell proliferation, migration, and apoptosis.
- To elucidate the molecular mechanism underlying XIST's function in bladder cancer.
Main Methods:
- Cell proliferation, cell cycle, and apoptosis assays were performed on bladder cancer cells.
- Cell migration was assessed using cell migration assays.
- RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays were used to examine the XIST-TET1 interaction and TET1's regulation of p53.
- Western blot analysis was conducted to detect p53 expression levels following XIST manipulation.
Main Results:
- Knockdown of XIST significantly inhibited cell migration and proliferation in vitro.
- The study confirmed that XIST binds to TET1.
- XIST was found to downregulate p53 expression through its interaction with TET1.
Conclusions:
- lncRNA XIST plays a role in bladder cancer progression.
- The XIST-TET1-p53 axis represents a potential regulatory network in bladder cancer.
- Targeting XIST may offer a therapeutic strategy for bladder cancer.
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