Page 22 - 南京医科大学学报自然科学版

南京医科大学学报（自然科学版） 第43卷第11期
·1494 · Journal of Nanjing Medical University（Natural Sciences） 2023年11月

·基础研究·

miR⁃449c通过抑制c⁃Myc的表达抑制肺腺癌细胞周期进程

娄 芮 ，朱佳浩 ，茆 勇 ，曹海霞 2*
1
1
1
江南大学附属医院肿瘤内科，江苏 无锡 214000；江苏省肿瘤医院（南京医科大学附属肿瘤医院）临床肿瘤实验中心，江苏
1 2
省肿瘤防治研究所，江苏 南京 210009

［摘 要］ 目的：探讨miR⁃449c对肺腺癌发生发展的影响及可能机制。方法：利用生物信息学分析鉴定高复发风险肺腺癌患
者（无病生存期≤6个月）与低复发风险患者（无病生存期＞60个月）之间差异表达的microRNA（miRNA）。靶基因预测及通路
分析研究可能的机制。RT⁃PCR检测miR⁃449c在肺腺癌组织和细胞系中的表达，利用细胞转染实验在肺腺癌细胞系中过表达
miR⁃449c和c⁃Myc，CCK⁃8法测定细胞增殖活性，流式细胞术检测细胞周期及凋亡，蛋白质印迹分析检测相关蛋白表达水平。
结果：生物信息学分析结果显示，相比低复发风险患者，肺腺癌高复发风险患者的miR⁃449c表达显著降低。miR⁃449c表达水
平与肺腺癌患者临床分期和淋巴结转移相关，miR⁃449c低表达患者的预后显著差于高表达患者。通路和功能分析表明，miR⁃
449c可能与细胞周期进程有关。与癌旁组织相比，miR⁃449c在肺腺癌组织中显著低表达；过表达miR⁃449c抑制了肺腺癌细胞
增殖，导致细胞周期阻滞于G1期，下调了c⁃Myc及其下游细胞周期蛋白的表达。c⁃Myc过表达可部分逆转miR⁃449c对细胞周
期蛋白的抑制，miR⁃449c过表达也可部分逆转c⁃Myc对细胞周期蛋白的上调。结论：miR⁃449c低表达的肺腺癌患者预后较差，过
表达miR⁃449c可以通过下调c⁃Myc调控细胞周期，抑制肺腺癌细胞增殖，提示miR⁃449c可能作为肺腺癌潜在的治疗靶标之一。
［关键词］ 肺腺癌；miR⁃449c；细胞周期；c⁃Myc
［中图分类号］ R734.2 ［文献标志码］ A ［文章编号］ 1007⁃4368（2023）11⁃1494⁃09
doi：10.7655/NYDXBNS20231103

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

1 1 1 2*
LOU Rui ，ZHU Jiahao ，MAO Yong ，CAO Haixia
2
1 Department of Oncology，the Affiliated Hospital of Jiangnan University，Wuxi 214000；Research Center for Clinical
Oncology，Jiangsu Cancer Hospital（the Affiliated Cancer Hospital of Nanjing Medical University），Jiangsu Institute
of Cancer Research，Nanjing 210009，China

［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.

［基金项目］ 江苏省卫计委科研项目（Z2018047）
∗
通信作者（Corresponding author），E⁃mail：pascallschx@126.com