Multi-Omics Analysis of the Therapeutic Value of MAL2 Based on Data Mining in Human Cancers

Jing Yuan; Xiaoyan Jiang; Hua Lan; Xiaoyu Zhang; Tianyi Ding; Fan Yang; Da Zeng; Jiahui Yong; Beibei Niu; Songshu Xiao

doi:10.3389/fcell.2021.736649

Multi-Omics Analysis of the Therapeutic Value of MAL2 Based on Data Mining in Human Cancers

Front Cell Dev Biol. 2022 Jan 17:9:736649. doi: 10.3389/fcell.2021.736649. eCollection 2021.

Authors

Jing Yuan¹, Xiaoyan Jiang¹, Hua Lan¹, Xiaoyu Zhang², Tianyi Ding², Fan Yang², Da Zeng¹, Jiahui Yong¹, Beibei Niu³, Songshu Xiao¹

Affiliations

¹ Department of Gynecology and Obstetrics, Third Xiangya Hospital, Central South University, Changsha, China.
² School of Life Science and Technology, Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University, Shanghai, China.
³ Scientific Research Center, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Recent studies have reported that T-cell differentiation protein 2 (MAL2) is an important regulator in cancers. Here, we downloaded data from multiple databases to analyze MAL2 expression and function in pan-cancers, especially in ovarian cancer (OC). Gene Expression Profiling Interactive Analysis (GEPIA) databases was used to examine MAL2 expression in 13 types of cancer. Kaplan-Meier plotter database was used to analyze the overall survival rate of MAL2 in pan-cancers. The Catalog of Somatic Mutations in Cancer (COSMIC), cBioPortal, and UCSC databases were used to examine MAL2 mutation in human cancers. Metascape, STRING, and GeneMANIA websites were used to explore MAL2 function in OC. Furthermore, ggplot2 package and ROC package were performed to analyze hub gene expression and undertake receiver operating characteristic (ROC) analysis. Drug sensitivity of MAL2 in OC was examined by the GSCALite database. In order to verify the results from databases above, real-time quantitative polymerase chain reaction (qRT-PCR) and western blotting were conducted to detect the expression of MAL2 in OC cells. CRISPR/Cas9 system was used to knockout the MAL2 gene in the OC cell lines HO8910 and OVCAR3, using specific guide RNA targeting the exons of MAL2. Then, we performed proliferation, colony formation, migration, and invasion assays to investigate the impact of MAL2 in OC cell lines in vivo and in vitro. Epithelial-mesenchymal transition (EMT)-associated biomarkers were significantly altered in vitro via western blotting and qRT-PCR. Taken together, we observed that MAL2 was remarkably dysregulated in multiple cancers and was related to patient overall survival (OS), mutation, and drug sensitivity. Furthermore, experimental results showed that MAL2 deletion negatively regulated the proliferation, migration, invasion, and EMT of OC, indicating that MAL2 is a novel oncogene that can activate EMT, significantly promote both the proliferation and migration of OC in vitro and in vivo, and provide new clues for treatment strategies.

Keywords: CRISPR/Cas9; T-cell differentiation protein 2 (MAL2); epithelial-mesenchymal transition (EMT); multi-omics; ovarian cancer; proliferation.