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Published on: March 30, 2019
Circular RNA NFIX Functions as an Oncogene in Non-Small Cell Lung Cancer by Modulating the miR-214-3p/TRIAP1 Axis
Guohua Liu1, Hanbing Shi1, Hongyan Zheng1
1Department of Respiratory and Critical Care Medicine, The Third Affiliated Hospital of Qiqihar Medical College, Qiqihar, China.
Background:
circRNA NFIX has been shown to exist as an oncogene in glioma. But its expression and role in NSCLC (non-small cell lung cancer) are still unclear. This research aimed to discover the expression and function of circRNA NFIX in NSCLC.
Methods:
In this research, qRT-PCR was utilized to investigate the expression levels of circRNA NFIX, miRNA-214-3p, and TRIAP1 in NSCLC tissues and cell lines. The binding sites between circRNA NFIX/TRIAP1 and miRNA-214-3p were predicted using the Starbase. These interactions were further validated using a double luciferase reporter assay. Cell proliferation and apoptosis were assessed through MTT and flow cytometry, respectively. The expression of apoptosis-related proteins was measured by western blot assay.
Results:
miRNA-214-3p could link with circRNA NFIX. circRNA NFIX was upregulated, while miRNA-214-3p was downregulated in NSCLC cell lines and clinical samples. Besides, suppression of circRNA NFIX repressed cell proliferation and induced apoptosis in NSCLC cells by upregulating miRNA-214-3p expression. Besides, the data indicated that TRIAP1 was a target of miRNA-214-3p, and it was negatively regulated by miRNA-214-3p in NSCLC cells. The excessive expression of miRNA-214-3p suppressed NSCLC cell proliferation and increased apoptosis. In addition, overexpression of TRIAP1 significantly reversed the effects on NSCLC cells caused by miRNA-214-3p mimic.
Conclusion:
circRNA NFIX silencing repressed the proliferation of NSCLC cells and induced cell apoptosis by regulating the miR-214-3p/TRIAP1 axis, which was a potential diagnostic and therapeutic target for NSCLC.
Insights
Circular RNA NFIX (circRNA NFIX) promotes non-small cell lung cancer (NSCLC) by downregulating miRNA-214-3p and upregulating TRIAP1. Silencing circRNA NFIX inhibits NSCLC cell proliferation and induces apoptosis.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Circular RNA NFIX (circRNA NFIX) is implicated as an oncogene in glioma.
- The expression and function of circRNA NFIX in non-small cell lung cancer (NSCLC) remain largely uncharacterized.
Purpose of the Study:
- To investigate the expression profile of circRNA NFIX in NSCLC.
- To elucidate the functional role of circRNA NFIX in NSCLC cell proliferation and apoptosis.
- To explore the molecular mechanism involving circRNA NFIX, miRNA-214-3p, and TRIAP1 in NSCLC.
Main Methods:
- Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to assess expression levels of circRNA NFIX, miRNA-214-3p, and TRIAP1.
- Bioinformatic prediction (Starbase) and dual-luciferase reporter assays to validate interactions between circRNA NFIX/TRIAP1 and miRNA-214-3p.
- MTT assays and flow cytometry to evaluate cell proliferation and apoptosis, respectively.
- Western blot analysis to measure apoptosis-related protein expression.
Main Results:
- circRNA NFIX was found to be upregulated, while miRNA-214-3p was downregulated in NSCLC tissues and cell lines.
- Suppression of circRNA NFIX inhibited NSCLC cell proliferation and induced apoptosis, correlating with increased miRNA-214-3p expression.
- TRIAP1 was identified as a target of miRNA-214-3p, with its expression negatively regulated by miRNA-214-3p. Overexpression of TRIAP1 reversed the effects of miRNA-214-3p mimic on NSCLC cells.
Conclusions:
- circRNA NFIX silencing inhibits NSCLC cell proliferation and induces apoptosis via the circRNA NFIX/miRNA-214-3p/TRIAP1 axis.
- This axis represents a potential diagnostic and therapeutic target for NSCLC.
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