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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Low expression of long non-coding RNA ARAP1-AS1 can inhibit lung cancer proliferation by inducing G0/G1 cell cycle
Xinlu Tao1,2, Yan Zhang2, Jiaping Li2
1Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
Background:
This paper examines the expression, function, and molecular mechanism of long non-coding ribonucleic acid (lncRNA) ARAP1 antisense RNA 1 (ARAP1-AS1) in lung cancer. Specifically, it aims to clarify the molecular mechanism of lncRNA ARAP1-AS1 that affects the occurrence and development of lung cancer, and provide a theoretical basis and molecular targets for targeted therapy or early diagnosis of lung cancer.
Methods:
Fluorescence quantitative detection of lncRNA ARAP1-AS1 expression in lung cancer tissues and cell lines, and methylthiazolyldiphenyl-tetrazolium (MTT), plate cloning experiment, and flow cytometry were used to detect the effect of knockdown of lncRNA ARAP1-AS1 on cell proliferation, clone formation, and the cell cycle, respectively. Western blotting was used to detect the expression of cell cycle-related proteins as well as the effect of knockdown of lncRNA ARAP1-AS1 on lung cancer. Cell proliferation was assessed by a nude mouse subcutaneous tumor formation experiment.
Results:
LncRNA ARAP1-AS1 is highly expressed in lung cancer tissues and cells. Knockdown of LncRNA ARAP1-AS1 can significantly inhibit the proliferation and clonal formation of lung cancer cells and induce G0/G1 cell cycle arrest. Knockdown of ARAP1-AS1 can markedly inhibit the expression of cell cycle-related protein cyclin D1, but has no significant effect on the expression of cyclin-dependent kinase (CDK)4 and CDK6. Furthermore, knockdown of ARAP1-AS1 can also notably inhibit the growth of lung cancer cells and substantially reduce the expression of Ki-67 in tumor-bearing tissues in nude mice.
Conclusions:
LncRNA ARAP1-AS1 is highly expressed in lung cancer. Knocking down of this gene can significantly inhibit cell proliferation in vitro and in vivo, and can also cause G0/G1 cell cycle arrest by inhibiting the expression of cyclin D1.
Insights
Long non-coding RNA ARAP1-AS1 is highly expressed in lung cancer. Inhibiting ARAP1-AS1 significantly reduces lung cancer cell proliferation and growth, offering potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Lung cancer is a leading cause of cancer-related mortality worldwide.
- Long non-coding RNAs (lncRNAs) are emerging as critical regulators in various cancers, including lung cancer.
- The specific role and molecular mechanisms of lncRNA ARAP1 antisense RNA 1 (ARAP1-AS1) in lung cancer remain largely unclear.
Purpose of the Study:
- To investigate the expression and function of lncRNA ARAP1-AS1 in lung cancer.
- To elucidate the molecular mechanism by which ARAP1-AS1 influences lung cancer development.
- To evaluate ARAP1-AS1 as a potential molecular target for lung cancer diagnosis and therapy.
Main Methods:
- Quantitative real-time PCR to assess ARAP1-AS1 expression in lung cancer tissues and cell lines.
- Cell proliferation assays (MTT, plate cloning) and flow cytometry to evaluate the impact of ARAP1-AS1 knockdown on cell cycle progression.
- Western blotting to analyze the expression of cell cycle-related proteins (cyclin D1, CDK4, CDK6).
- Nude mouse xenograft models to assess the in vivo effect of ARAP1-AS1 knockdown on tumor growth.
Main Results:
- ARAP1-AS1 was found to be significantly upregulated in lung cancer tissues and cell lines.
- Knockdown of ARAP1-AS1 markedly inhibited lung cancer cell proliferation and colony formation in vitro.
- ARAP1-AS1 knockdown induced G0/G1 phase cell cycle arrest and reduced cyclin D1 expression.
- In vivo studies demonstrated that ARAP1-AS1 knockdown suppressed tumor growth and decreased Ki-67 expression in tumor tissues.
Conclusions:
- LncRNA ARAP1-AS1 is oncogenic and overexpressed in lung cancer.
- Downregulation of ARAP1-AS1 inhibits lung cancer cell proliferation and tumor growth both in vitro and in vivo.
- ARAP1-AS1 may promote lung cancer progression by regulating the cell cycle, specifically through cyclin D1 inhibition.
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