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LINC00426, a novel m6A-regulated long non-coding RNA, induces EMT in cervical cancer by binding to ZEB1
Siyuan Shen1, Hua Jin2, Xing Zhang1
1Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
Purpose:
To explore the function and molecular mechanism of LINC00426 in Cervical Cancer (CC), and to explore the clinical treatment strategy of LINC00426 for CC.
Methods:
Bioinformatics analysis was used to explore the expression of LINC00426 and patient prognosis of CC. Cell function experiments were conducted to explore the potential effect of LINC00426 on CC malignant phenotypes. The difference in m6A modification level between the high and low expression groups of LINC00426 was analyzed by detecting the total m6A level. The luciferase reporter assay was used to confirm the binding of miR-200a-3p to LINC00426. The RIP assay was used to confirm the binding of LINC00426 to ZEB1. Cell viability assay was performed to detect the effect of LINC00426 on cellular drug resistance.
Results:
LINC00426 is up-regulated in CC, which can enhance the proliferation, migration and invasion of CC cells. METTL3 promotes the expression of LINC00426 by m6A methylation modification. In addition, the LINC00426/miR-200a-3p/ZEB1 axis affects the proliferation, migration, and invasion of CC by regulating the expression of EMT markers. Through the detection of cell viability, we observed that overexpression LINC00426 in cells resulted in resistance to cisplatin and bleomycin, and more sensitive to imatinib.
Conclusion:
LINC00426 is a cancer-promoting lncRNA related to m6A modification. The process of EMT in CC is regulated by the LINC00426/miR-200a/3p/ZEB1 axis. LINC00426 can affect the sensitivity of CC cells to chemotherapy drugs, and is expected to become a therapeutic target for CC.
Insights
LINC00426 promotes cervical cancer (CC) progression and drug resistance via m6A modification and the miR-200a-3p/ZEB1 axis. This lncRNA is a potential therapeutic target for CC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Cervical cancer (CC) remains a significant global health challenge.
- Understanding the molecular mechanisms driving CC progression is crucial for developing effective therapies.
Purpose of the Study:
- To elucidate the function and molecular mechanism of LINC00426 in CC.
- To investigate LINC00426 as a potential therapeutic target for CC.
Main Methods:
- Bioinformatics analysis of LINC00426 expression and patient prognosis.
- In vitro cell function experiments to assess malignant phenotypes.
- m6A modification analysis, luciferase reporter assays, and RIP assays to determine molecular interactions.
- Cell viability assays to evaluate drug resistance.
Main Results:
- LINC00426 is upregulated in CC, enhancing cell proliferation, migration, and invasion.
- METTL3-mediated m6A modification promotes LINC00426 expression.
- The LINC00426/miR-200a-3p/ZEB1 axis regulates epithelial-mesenchymal transition (EMT) in CC.
- Overexpression of LINC00426 confers resistance to cisplatin and bleomycin, and sensitivity to imatinib.
Conclusions:
- LINC00426 acts as an oncogenic long noncoding RNA (lncRNA) in CC, linked to m6A modification.
- The LINC00426/miR-200a-3p/ZEB1 pathway is a key regulator of EMT in CC.
- LINC00426 influences CC cell sensitivity to chemotherapy drugs, presenting a promising therapeutic target.
Related Concept Videos
lncRNA - Long Non-coding RNAs
Master Transcription Regulators
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Non-LTR Retrotransposons
Inheritance of Chromatin Structures
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