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Published on: March 30, 2019
Circ_0016760 Serves as a Cancer Promoter in Non-small Cell Lung Cancer Through miR-876-3p/NOVA2 Axis
Fengjie Liu1, Haiying Gao1, Mingwei Chen2
1Department of General Practice, The Second Affiliated Hospital of Dalian Medical University, No.467, Zhongshan Road, Dalian, 116027, Liaoning, China.
Abstract:
Non-small cell lung cancer (NSCLC) is a serious threaten to human health globally. Circular RNAs (circRNAs) were testified to alter the progression of NSCLC. This work intended to investigate the functional role of circ_0016760 in NSCLC development and the potential mechanism. Expression of circ_0016760, microRNA (miR)-876-3p and NOVA alternative splicing regulator 2 (NOVA2) was determined via quantitative reverse transcription-PCT (qRT-PCR) or western blotting. Cell viability, clonogenicity and apoptosis were assessed by Cell Counting Kit-8 (CCK-8) assay, colony formation assay and flow cytometry, respectively. Transwell assay was performed to examine cell migration and invasion. Western blotting was also conducted to detect the levels of epithelial-to-mesenchymal transition (EMT)-related proteins. Role of circ_0016760 in vivo was evaluated via xenograft model assay. Moreover, the interaction between miR-876-3p and circ_0016760 or NOVA2 was verified by dual-luciferase reporter assay or RNA Immunoprecipitation (RIP) assay. Circ_0016760 and NOVA2 were upregulated, while miR-876-3p expression was decreased in NSCLC tissues and cells. Circ_0016760 depletion suppressed NSCLC cell proliferation and metastasis in vitro, as well as hampered tumor growth in vivo. Circ_0016760 acted as a sponge of miR-876-3p, and miR-876-3p could target NOVA2. Circ_0016760 might play vital roles in NSCLC by regulating miR-876-3p/NOVA2 axis. Circ_0016760 could promote the malignant development of NSCLC through miR-876-3p/NOVA2 axis, at least in part.
Insights
Circular RNA circ_0016760 promotes non-small cell lung cancer (NSCLC) progression by sponging miR-876-3p, which targets NOVA2. This circRNA/miRNA/mRNA axis drives NSCLC development and malignancy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) poses a significant global health challenge.
- Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer progression, including NSCLC.
Purpose of the Study:
- To investigate the functional role of circ_0016760 in NSCLC development.
- To elucidate the underlying molecular mechanism involving miR-876-3p and NOVA2.
Main Methods:
- Quantitative reverse transcription-PCR (qRT-PCR) and western blotting for expression analysis.
- In vitro assays (CCK-8, colony formation, Transwell) for proliferation, apoptosis, migration, and invasion.
- In vivo xenograft model for tumor growth evaluation.
- Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays for interaction verification.
Main Results:
- Circ_0016760 and NOVA2 were upregulated, while miR-876-3p was downregulated in NSCLC tissues and cells.
- Circ_0016760 depletion inhibited NSCLC cell proliferation, metastasis, and tumor growth.
- Circ_0016760 acts as a molecular sponge for miR-876-3p, which directly targets NOVA2.
Conclusions:
- Circ_0016760 promotes NSCLC malignancy by regulating the miR-876-3p/NOVA2 axis.
- Circ_0016760 is a potential therapeutic target for NSCLC treatment.
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