食管癌中miRNA枢纽靶基因的鉴定和验证

doi:10.13418/j.issn.1001-165x.2025.1.09

中国临床解剖学杂志 ›› 2025, Vol. 43 ›› Issue (1): 54-62.doi: 10.13418/j.issn.1001-165x.2025.1.09

食管癌中miRNA枢纽靶基因的鉴定和验证

赵婷婷¹，宋爽¹，石科²，李晓英¹，李攀阳¹，李宁宁³*

1.河南医学高等专科学校组织学与胚胎学教研室，河南郑州 451191； 2.河南医学高等专科学校生物化学教研室，河南郑州 451191； 3.河南医学高等专科学校病理学教研室，河南郑州 451191

收稿日期:2024-08-12 出版日期:2025-01-25 发布日期:2025-01-22
通讯作者: 李宁宁，副教授，主要研究方向：肿瘤分子病理，E-mail: ningning0703@126.com
作者简介:赵婷婷（1988-），女，硕士，讲师，主要研究方向：肿瘤分子生物学，E-mail: 906360769@qq.com
基金资助:
河南省科技攻关项目（232102310220）；河南省高等学校重点科研项目（23A320068）；河南省医学科技攻关项目（项目编号:LHGJ20220707）

Identification and validation of miRNA hub target genes in esophageal cancer

Zhao Tingting ¹, Song Shuang ¹, Shi Ke², Li Xiaoying¹, Li Panyang ¹, Li Ningning³*

1. Department of Histology and Embryology, Henan Medical College, Zhengzhou 451191, China; 2. Department of Biochemistry, Henan Medical College, Zhengzhou 451191, China; 3. Department of Pathology, Henan Medical College, Zhengzhou 451191, China

Received:2024-08-12 Online:2025-01-25 Published:2025-01-22

摘要/Abstract

摘要： 目的探讨与食管癌发生发展相关的miRNAs-mRNAs，研究PALB2对人食管癌EC109细胞生物学性状的影响。方法从GEO和TCGA数据库下载食管癌miRNAs数据集筛选交集，通过starbase数据库预测交集miRNAs的潜在靶基因，并使用PPI网络分析确定枢纽靶基因；对靶基因和枢纽靶基因分别进行GO和KEGG功能富集分析。选择预后差异显著的PALB2基因进行细胞试验，合成PALB2的特异性RNA(si-PALB2)转染EC109细胞，RT-qPCR检测细胞中PALB2的表达量，MTT、Transwell和流式分析PALB2对细胞活力、侵袭迁移和凋亡能力的影响；Western blot检测细胞周期蛋白CyclinD1、凋亡抑制蛋白Bcl-2和基质金属蛋白酶MMP-9的表达变化。结果生物信息学分析预测了参与食管癌发生发展的重要miRNAs-mRNAs，并通过实验验证敲降PALB2的表达后，EC109细胞活力、侵袭转移能力均明显降低，凋亡能力明显增加，cyclinD1、Bcl-2及MMP-9表达均明显下调。结论 MiRNAs-mRNAs是预测食管癌发生发展的生物标志物；PALB2在食管癌中发挥促癌作用，与调控细胞周期蛋白、抗凋亡蛋白及侵袭转移相关蛋白密切相关，是诊断和治疗的潜在靶点。

关键词: 生物信息学分析, , , miRNA, , , 食管癌, , , PALB2

Abstract: Objective To investigate miRNAs-mRNAs related to the occurrence and development of esophageal cancer, and study the effect of PALB2 on the biological characters of human esophageal cancer EC109 cells. Methods The data of esophageal cancer miRNAs were downloaded from GEO and TCGA databases to screen out the intersecting miRNAs. The potential target genes of intersection were predicted by starbase database, and the key target genes were identified by PPI network analysis. Functional enrichment analysis was performed for differential genes and hub target genes in GO and KEGG databases. PALB2 gene with significant prognostic difference was selected for cell test, and PALB2 specific small interfering RNA (si-PALB2) was synthesized and transfected into EC109 cells. The expression level of PALB2 in the cells was detected by RT-qPCR. The effects of PALB2 on cell viability, invasion, migration and apoptosis were investigated by MTT, Transwell and flow cytometry. The expression of cyclin CyclinD1, apoptosis suppressor Bcl-2 and matrix metalloproteinase MMP-9 were detected by Western blot. Results Bioinformatics analysis showed that miRNAs-mRNAs were involved in the development of esophageal cancer. After PALB2 knockdown, EC109 cell viability, invasion and metastasis ability were significantly decreased, apoptosis ability was significantly increased, and the expressions of cyclinD1, Bcl-2 and MMP-9 were significantly down-regulated. Conclusions MiRNAs-mRNAs are biomarkers for predicting the development of esophageal cancer. PALB2 plays a role in promoting cancer in esophageal cancer, and is closely related to the regulation of cyclin, anti-apoptotic protein and invasion and metastasis related protein, which is a potential target for diagnosis and treatment.

Key words: Bioinformatics analysis, , , miRNA, , , Esophageal cancer, , , PALB2

中图分类号:

R735.

赵婷婷, 宋爽, 石科, 李晓英, 李攀阳, 李宁宁. 食管癌中miRNA枢纽靶基因的鉴定和验证[J]. 中国临床解剖学杂志, 2025, 43(1): 54-62.

Zhao Tingting, Song Shuang, Shi Ke, Li Xiaoying, Li Panyang, Li Ningning. Identification and validation of miRNA hub target genes in esophageal cancer[J]. Chinese Journal of Clinical Anatomy, 2025, 43(1): 54-62.

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食管癌中miRNA枢纽靶基因的鉴定和验证

Identification and validation of miRNA hub target genes in esophageal cancer

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