Identification of invasion-metastasis associated MiRNAs in gallbladder cancer by bioinformatics and experimental validation

被引：12

作者：

Cao, Jiasheng ^{[1
,2
]}

Shao, Huijiang ^{[2
,3
]}

Hu, Jiahao ^{[1
,2
]}

Jin, Renan ^{[1
,2
]}

Feng, Anyun ^{[4
]}

Bin Zhang ^{[1
,2
]}

Li, Shijie ^{[1
,2
]}

Chen, Tianen ^{[1
,2
]}

Jeungpanich, Sarun ^{[2
]}

Topatana, Win ^{[2
]}

Tian, Yitong ^{[2
]}

Lu, Ziyi ^{[2
]}

Cai, Xiujun ^{[1
,2
]}

Chen, Mingyu ^{[1
,2
]}

机构：

[1] Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Gen Surg, 3 East Qingchun Rd, Hangzhou 310016, Zhejiang, Peoples R China

[2] Zhejiang Univ, Sch Med, Hangzhou 310058, Zhejiang, Peoples R China

[3] Shaoxing Peoples Hosp, Dept Hepatobiliary & Pancreat Surg, Shaoxing 312000, Zhejiang, Peoples R China

[4] Zhejiang Univ, Affiliated Hosp 1, Coll Med, Hlth Management Ctr, Hangzhou 310022, Peoples R China

来源：

JOURNAL OF TRANSLATIONAL MEDICINE | 2022年 / 20卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Gallbladder cancer; MiRNA; Invasion; Metastasis; Bioinformatics; EXPRESSION; MICRORNAS; GENES;

D O I：

10.1186/s12967-022-03394-8

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Background: Recent studies exploring the roles of invasion-metastasis associated miRNAs in gallbladder cancer (GBC) are limited. In the study, we aimed to identify the invasion-metastasis associated miRNAs in GBC by bioinformatics and experimental validation. Methods: MiRNAs of different expression were identified by comparing GBC tumor samples with different survival from Gene Expression Omnibus database. MiRTarBase was used for identifying the potential target genes of miRNAs. Then, we performed Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. And miRNA-gene and protein-protein interaction (PPI) network were constructed for hub genes evaluation. We further explored and compared miR-642a-3p and miR-145-5p expression in both The Cancer Genome Atlas database and our hospital data. Finally, quantitative real-time PCR, wound healing assay, and Transwell assay were conducted to validate the invasion-metastasis associated miRNAs in GBC. Results: In GSE104165 database, 25 up-regulated and 97 down-regulated miRNAs were detected with significantly different expression in GBC tumor samples. Then, 477 potential target genes were identified from the 2 most up-regulated miRNAs (miR-4430 and miR-642a-3p) and 268 genes from the 2 most down-regulated miRNAs (miR-451a and miR-145-5p). After GO and KEGG analysis, mTOR and PI3K-Akt signaling pathways were found associated with the potential target genes. Based on PPI network, the top 10 highest degree hub nodes were selected for hub genes. Furthermore, the miRNA-hub gene network showed significant miR-642a-3p up-regulation and miR-145-5p down-regulation in both GBC tissues and cell lines. In the experimental validation, miR-145-5p up-regulation and miR-642a-3p down-regulation were confirmed to suppress GBC invasion and metastasis. Conclusions: MiR-642a-3p and miR-145-5p were identified as invasion-metastasis associated miRNAs via bioinformatics and experimental validation, and both up-regulation of miR-642a-3p and down-regulation of miR-145-5p would be served as novel treatment options for GBC in the future.

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