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      MiroRNA-31-3p Promotes the Invasion and Metastasis of Non-Small-Cell Lung Cancer Cells by Targeting Forkhead Box 1 (FOXO1)

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          Abstract

          Objective

          To explore the possibility of microRNA miR-31-3p as a biomarker for bone metastasis of non-small-cell lung cancer (NSCLC) and its molecular mechanism to the invasion and metastasis of NSCLC cells.

          Methods

          Real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of miR-31-3p and forkhead box 1 (FOXO1) in NSCLC tissues, serum, and cells to analyze the correlation between the expression levels of miR-31-3p and the clinicopathology of NSCLC. After interference with or overexpressing miR-31-3p, NSCLC cell proliferation, apoptosis, invasion ability, and migration ability were detected by MTT, flow cytometry, Transwell, and scratch experiment, respectively. The interaction between miR-31-3p and FOXO1 was further verified by the dual-luciferase reporter experiment. Western blot was performed to detect the protein expression of FOXO1 in tissues and FOXO1, RhoA, p-RhoA, ROCK-2, and p-ROCK-2 in cells.

          Results

          In tissues, serum, and NSCLC cell line A549 of the NSCLC patients, the expression of FOXO1 was notably lower, and the miR-31-3p expression was significantly higher. Overexpression of miR-31-3p could distinctly improve the proliferation, invasion, and migration of A549 cells, meanwhile inhibit cell apoptosis, and activate the RhoA/ROCK-2 signaling pathway, while interfering with the expression of miR-31-3p has the opposite function. Besides, bioinformatics analysis and luciferase reporter assay confirmed that FOXO1 was a target gene of miR-31-3p. Overexpressing FOXO1 could inhibit the proliferation and metastasis of A549 cells, but overexpressing miR-31-3p reverses the results.

          Conclusion

          This study confirmed that miR-31-3p promotes the proliferation, invasion, and migration of NSCLC cells and inhibits apoptosis through targeted regulating FOXO1 and be a potential therapeutic targets for the treatment of NSCLC.

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          Most cited references44

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          MicroRNAs: genomics, biogenesis, mechanism, and function.

          MicroRNAs (miRNAs) are endogenous approximately 22 nt RNAs that can play important regulatory roles in animals and plants by targeting mRNAs for cleavage or translational repression. Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
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            MicroRNA therapeutics: towards a new era for the management of cancer and other diseases

            MicroRNAs (miRNAs) are small non-coding RNAs that can modulate mRNA expression. Insights into the roles of miRNAs in development and disease have led to the development of new therapeutic approaches that are based on miRNA mimics or agents that inhibit their functions (antimiRs), and the first such approaches have entered the clinic. This Review discusses the role of different miRNAs in cancer and other diseases, and provides an overview of current miRNA therapeutics in the clinic.
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              MicroRNAs

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                Author and article information

                Contributors
                Journal
                Comput Math Methods Med
                Comput Math Methods Med
                cmmm
                Computational and Mathematical Methods in Medicine
                Hindawi
                1748-670X
                1748-6718
                2022
                27 January 2022
                : 2022
                : 4597087
                Affiliations
                Department of Respiratory Medicine, Changsha Central Hospital Affiliated to Nanhua University, Hunan, China
                Author notes

                Academic Editor: Osamah Ibrahim Khalaf

                Author information
                https://orcid.org/0000-0003-4967-3081
                Article
                10.1155/2022/4597087
                8813222
                35126623
                9dee3bca-58f6-431d-8fab-e1f740614436
                Copyright © 2022 Xiaoyuan Zeng et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 October 2021
                : 5 December 2021
                : 8 December 2021
                Funding
                Funded by: Application for scientific research project of Hunan Provincial Health and Family Planning Commission
                Award ID: B2017205
                Categories
                Research Article

                Applied mathematics
                Applied mathematics

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