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TFPI2AS1, a novel lncRNA that inhibits cell proliferation and migration in lung cancer
Shenglan Gao1, Ziying Lin1, Chunyan Li1
1a Clinical Research Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang , China.
Abstract:
Accumulating evidence demonstrates that a series of differentially expressed lncRNAs is important in tumorigenesis. However, the function of many of the lncRNAs in lung cancer remains elusive. In the present study, we used microarray analysis to identify lncRNAs that are dysregulated in non-small-cell lung cancer (NSCLC) as compared with normal tissues. Among the dysregulated lncRNAs, we identified TFPI2AS1, an antisense transcript of the tumor suppressor TFPI2 (tissue factor pathway inhibitor 2). TFPI2AS1 was shown to be markedly upregulated in NSCLC patient tumors as compared to paired non-tumor samples. TFPI2AS1 knockdown increased NSCLC cell proliferation and migration, which was associated with enhanced G1/S transition and downregulation of cyclin D1 and cyclin-dependent kinases 2 (CDK2), while TFPI2AS1 overexpression had the opposite effect. Knockdown and overexpression experiments also suggested that TFPI2AS1 regulates NSCLC cell migration and AKT activation. Moreover, TFPI2AS1 is a positive regulator of TFPI2. Our findings bring new insights for understanding the role of TFPI2AS1 in mediating the proliferation and migration of NSCLC cells by regulating TFPI2 expression.
Insights
TFPI2AS1, a long non-coding RNA, is upregulated in non-small cell lung cancer (NSCLC). Its knockdown promotes NSCLC cell growth and migration, while its overexpression inhibits these processes, offering new therapeutic insights.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) play critical roles in tumorigenesis, but their specific functions in lung cancer are not fully understood.
- Identifying novel dysregulated lncRNAs in non-small cell lung cancer (NSCLC) is crucial for understanding cancer progression.
Purpose of the Study:
- To identify dysregulated lncRNAs in NSCLC using microarray analysis.
- To investigate the function of the identified lncRNA, TFPI2AS1, in NSCLC cell proliferation and migration.
- To elucidate the regulatory relationship between TFPI2AS1 and the tumor suppressor TFPI2.
Main Methods:
- Microarray analysis to identify differentially expressed lncRNAs in NSCLC tissues.
- In vitro experiments involving TFPI2AS1 knockdown and overexpression in NSCLC cell lines.
- Cell proliferation and migration assays.
- Western blotting to assess protein levels (e.g., cyclin D1, CDK2, AKT, TFPI2).
Main Results:
- TFPI2AS1 was significantly upregulated in NSCLC tumors compared to non-tumor samples.
- TFPI2AS1 knockdown enhanced NSCLC cell proliferation and migration, linked to G1/S transition and altered cyclin D1/CDK2 levels.
- TFPI2AS1 overexpression inhibited NSCLC cell proliferation and migration.
- TFPI2AS1 was found to regulate AKT activation and is a positive regulator of TFPI2 expression.
Conclusions:
- TFPI2AS1 is a key regulator of NSCLC cell proliferation and migration.
- TFPI2AS1 exerts its effects, at least in part, by modulating TFPI2 expression.
- TFPI2AS1 represents a potential therapeutic target for NSCLC.
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