miR⁃449c inhibits the cell cycle progression of lung adenocarcinoma cells by inhibiting the expression of c⁃Myc
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R734.2

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    Abstract:

    Objective:The purpose of the current study was to explore the effect and possible mechanism of miR-449c on the occurrence and development of lung adenocarcinoma. Methods:Bioinformatics analysis was used to identify the differentially expressed microRNAs between samples with lung adenocarcinoma patients at a high risk of recurrence(disease-free survival ≤6 months)and samples with lung adenocarcinoma patients at a low risk of recurrence(disease -free survival >60 months). Target gene prediction and pathway analysis were used to analysis possible mechanisms. RT-PCR was used to detect the expression of miR-449c in lung adenocarcinoma tissues and cell lines. miR-449c and c-Myc were overexpressed in lung adenocarcinoma cell lines by cell transfection experiments. Cell growth activity was determined by CCK-8. Cell cycle and apoptosis were detected by flow cytometry. Western blot analysis was used for relevant protein expression. Results:The results of bioinformatics analysis showed that the expression of miR-449c was significantly decreased in the group of lung adenocarcinoma patients at a high risk of recurrence, compared with that at a low risk of recurrence. The expression of miR-449c was significantly correlated with the clinical stage and lymph node metastasis of patients with lung adenocarcinoma. The prognosis of patients with low miR-449c expression was significantly worse than that of patients with high miR-449c expression. Pathway and functional analysis indicated that miR-449c may be involved in cell cycle progression. Compared with normal tissues,miR-449c was significantly lower expressed in lung adenocarcinoma tissues.Overexpression of miR-449c inhibited lung adenocarcinoma cell proliferation,resulted in cell cycle arrest in G1 phase,and downregulated the expression of c-Myc and its downstream cyclins. Overexpression of c-Myc could partially counteract the inhibition of cyclin by miR -449c. Overexpression of miR-449c could also partially counteract the up-regulation of cyclin expression by c -Myc. Conclusion:Lung adenocarcinoma patients with low expression of miR-449c have a poor prognosis. Overexpression of miR-449c can regulate the lung adenocarcinoma cell cycle by downregulating c -Myc to inhibit the proliferation of lung adenocarcinoma cells. The results suggest that miR-449c may be one of the potential therapeutic targets for lung adenocarcinoma.

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娄芮,朱佳浩,茆勇,曹海霞. miR⁃449c通过抑制c⁃Myc的表达抑制肺腺癌细胞周期进程[J].南京医科大学学报(自然科学版英文版),2023,(11):1494-1502.

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  • Received:March 01,2023
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  • Online: November 17,2023
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