Association Mining Identifies MAL2 as a Novel Tumor Suppressor in Colorectal Cancer

Kailai Wang; Yanmei Yang; Shu Zheng; Wangxiong Hu

doi:10.2147/OTT.S369670

Association Mining Identifies MAL2 as a Novel Tumor Suppressor in Colorectal Cancer

Onco Targets Ther. 2022 Jul 9:15:761-769. doi: 10.2147/OTT.S369670. eCollection 2022.

Authors

Kailai Wang^#¹, Yanmei Yang^#², Shu Zheng¹, Wangxiong Hu¹

Affiliations

¹ Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People's Republic of China.
² Key Laboratory of Reproductive and Genetics, Ministry of Education, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, People's Republic of China.

^# Contributed equally.

Abstract

Introduction: Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. However, the driver genes that promote CRC metastasis remain poorly understood. Association mining mines and extracts the repeated correlations and relevance in a dataset to predict the appearance of other data items according to the appearance of one item.

Methods: Here, the Apriori algorithm was used to find the frequent mutational gene sets (FMGSs) and hidden association rules (ARs) within these FMGSs from 383 CRCs with whole exome sequencing datasets. The weighted correlation network analysis (WGCNA) was used to identify the hub genes in CRC. CCK8, colony formation, cell migration and invasion assays were adopted to detect the roles of hub genes in CRC.

Results: Intriguingly, we found that MAL2 (myelin and lymphocyte protein 2) was associated with TP53 and APC in stage IV of CRC, and further subnetwork exploration based on WGCNA identified MAL2 as a potent hub gene. To validate the metastasis-related role of MAL2 in CRC, a lentivirus-based overexpression system was utilized to construct MAL2-overexpressing human CRC LOVO cells. Overexpression of MAL2 remarkably inhibited CRC cell proliferation and invasion.

Conclusion: Our results highlighted that MAL2 acts as a tumor suppressor in CRC and could serve as a potential therapeutic target.

Keywords: Apriori; CRC; MAL2; frequent mutational gene sets.

Grants and funding

This work was supported by the National Natural Science Foundation of China (grant number 81802883) and Fundamental Research Funds for the Central Universities (grant number 2018FZA7012) to Wangxiong Hu.