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

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.

The MAL Family of Proteins: Normal Function, Expression in Cancer, and Potential Use as Cancer Biomarkers

“…In aggressive clones of the SH-SY5Y human neuroblastoma cell line, copy number gain of MAL2 resulted in increased expression of MAL2 transcripts [107]. The analysis with cBioportal tools indicates that the percentage of MAL2 CNAs is positively correlated with the level of MAL2 transcripts in cancer (Figure S2), as was noted previously [131]. The correlation was less strict for the other MAL-family genes (Figure S2).…”

“…However, overexpression of MAL2 in a colorectal cell line inhibited cell proliferation and invasion and suppressed tumorigenesis in xenograft in the same models [154], indicating that the role of MAL2 in cancer progression might be tissue-dependent. An effect of MAL2 silencing on cell proliferation, similar to that in lung cancer cell lines, was observed in breast [96], ovarian [131], pancreatic [148] and prostate [155] cancer cell lines, in which migration and invasion and the epithelial-to-mesenchymal transition were decreased. MAL2 silencing also affected tumor size in nude mice xenografts of pancreatic cancer cells [155].…”

“…It is interesting to note that, although MAL is hypomethylated and is normally expressed in OV and ovarian cancer cell lines, its expression is upregulated in response to treatment of ovarian cancer cell lines with 5-aza-2 -deoxycytidine, indicating that the methylated region at the promoter region regulates MAL expression [130]. Hypomethylation was also found in MAL2 in OV [131]. The expression of each MAL-family gene in the indicated type of cancer is compared with that in adjacent normal tissue.…”

Cold atmospheric plasma sensitizes head and neck cancer to chemotherapy and immune checkpoint blockade therapy

“…CAP PZ2 down-regulates these markers in Fadu, Cal27, A375, and Hth83 cells. EMT affects tumor cell invasion and metastasis [ 68 ]. E-Cadherin and N-Cadherin are markers of EMT and tumor progression [ 69 ].…”

Construction and validation of a novel prognostic model for thyroid cancer based on N7-methylguanosine modification-related lncRNAs

“…To further investigate the regulatory relationship between prognostic DEm7G-lncRNAs (PDEm7G-lncRNAs) and mRNAs, we inputted regulatory network parameters and the list of PDEm7G-lncRNAs into R software to establish a regulatory network linked by lncRNAs and their target genes and visualized them with a Sankey diagram using the packages ggalluvial, ggplot2, and dplyr. [ 21 , 22 ]…”