Long noncoding RNA XIST acts as an oncogene in non-small cell lung cancer by epigenetically repressing KLF2
Jing Fang1, Cheng-Cao Sun2, Cheng Gong3
1Department of Oncology, Wuhan Pu-Ai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430034, PR China.
Abstract:
Recently, long noncoding RNAs (lncRNAs) have been identified as critical regulators in numerous types of cancers, including non-small cell lung cancer (NSCLC). X inactivate-specific transcript (XIST) has been found to be up-regulated and acts as an oncogene in gastric cancer and hepatocellular carcinoma, but little is known about its expression pattern, biological function and underlying mechanism in NSCLC. Here, we identified XIST as an oncogenic lncRNA by driving tumorigenesis in NSCLC. We found that XIST is over-expressed in NSCLC, and its increased level is associated with shorter survival and poorer prognosis. Knockdown of XIST impaired NSCLC cells proliferation, migration and invasion in vitro, and repressed the tumorigenicity of NSCLC cells in vivo. Mechanistically, RNA immune-precipitation (RIP) and RNA pull-down experiment demonstrated that XIST could simultaneously interact with EZH2 to suppress transcription of its potential target KLF2. Additionally, rescue experiments revealed that XIST's oncogenic functions were partly depending on silencing KLF2 expression. Collectively, our findings expound how XIST over-expression endows an oncogenic function in NSCLC.
Insights
Long noncoding RNAs (lncRNAs) like XIST promote non-small cell lung cancer (NSCLC) growth. Silencing XIST inhibits NSCLC progression by regulating KLF2 expression, offering a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long noncoding RNAs (lncRNAs) are key regulators in cancer.
- XIST, an oncogenic lncRNA in other cancers, has an unknown role in non-small cell lung cancer (NSCLC).
Purpose of the Study:
- To investigate the role and mechanism of XIST in NSCLC tumorigenesis.
Main Methods:
- Quantitative real-time PCR to assess XIST expression.
- In vitro assays (proliferation, migration, invasion) and in vivo tumorigenicity assays.
- RNA immunoprecipitation (RIP) and RNA pull-down assays to identify molecular interactions.
- Rescue experiments to validate mechanistic findings.
Main Results:
- XIST was over-expressed in NSCLC tissues and correlated with poor prognosis.
- XIST knockdown suppressed NSCLC cell proliferation, migration, invasion, and in vivo tumor growth.
- XIST directly interacted with EZH2 to suppress KLF2 transcription.
- KLF2 silencing partially mediated XIST's oncogenic functions.
Conclusions:
- XIST acts as an oncogenic lncRNA in NSCLC by suppressing KLF2 via EZH2.
- XIST is a potential therapeutic target for NSCLC treatment.
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