BCL2L1 is regulated by the lncRNA MIR4435-2HG-miR-513a-5p-BCL2L1 ceRNA axis and serves as a biomarker for pancreatic adenocarcinoma treatment and prognosis

Abstract

Pancreatic adenocarcinoma (PAAD) is one of the most malignant cancers. After escaping death, cancer cells are made more metastatic, aggressive, and also drug-resistant through anoikis resistance. The aim of this study is to explore the molecular mechanisms of anoikis-related genes in PAAD and to identify potential key biomarkers. We integrated information about PAAD from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) databases and identified anoikis-related gene BCL2L1 by survival analysis, univariate Cox regression analysis, and multifactorial Cox regression analysis. Various bioinformatics approaches showed that BCL2L1 was a valuable prognostic marker that might be involved in PAAD development and progression through different mechanisms, including cancer intervention, genomic heterogeneity, and RNA modifications. Our analysis showed that BCL2L1 expression also closely correlates with the expression of various immune checkpoint inhibitors. In particular, we found that long non-coding RNA MIR4435-2HG acted as ceRNA sponging miR-513a-5p to promote the expression of BCL2L1, thereby promoting pancreatic cancer cells proliferation. In conclusion, BCL2L1 expression regulated by the MIR4435-2HG-miR-513a-5p-BCL2L1 ceRNA axis might be used as a biomarker for cancer prognosis, treatment selection, and follow-up in PAAD patients.