In silico analysis to identify novel ceRNA regulatory axes associated with gallbladder cancer

Abstract

Competitive endogenous RNA (ceRNA) networks are reported to play a crucial role in regulating cancer-associated genes. Identification of novel ceRNA networks in gallbladder cancer (GBC) may improve the understanding of its pathogenesis and might yield useful leads on potential therapeutic targets for GBC. For this, a literature survey was done to identify differentially expressed lncRNAs (DELs), miRNAs (DEMs), mRNAs (DEGs) and proteins (DEPs) in GBC. Ingenuity pathway analysis (IPA) using DEMs, DEGs and DEPs in GBC identified 242 experimentally observed miRNA-mRNA interactions with 183 miRNA targets, of these 9 (CDX2, MTDH, TAGLN, TOP2A, TSPAN8, EZH2, TAGLN2, LMNB1, and PTMA) were reported at both mRNA and protein levels. Pathway analysis of 183 targets revealed p53 signaling among the top pathway. Protein-protein interaction (PPI) analysis of 183 targets using the STRING database and cytoHubba plug-in of Cytoscape software revealed 5 hub molecules, of which 3 of them (TP53, CCND1 and CTNNB1) were associated with the p53 signaling pathway. Further, using Diana tools and Cytoscape software, novel lncRNA-miRNA-mRNA networks regulating the expression of TP53, CCND1, CTNNB1, CDX2, MTDH, TOP2A, TSPAN8, EZH2, TAGLN2, LMNB1, and PTMA were constructed. These regulatory networks may be experimentally validated in GBC and explored for therapeutic applications.

Overcoming MTDH and MTDH-SND1 complex: driver and potential therapeutic target of cancer

“…Meanwhile, high expression of MTDH was associated with distant metastasis of colorectal cancer and survival of patients after surgery. Moreover, based on clinical patient samples, a large number of studies have found that high expression of MTDH was significantly associated with postoperative survival rate, tumor metastasis, clinical stage progression and tumor angiogenesis in HCC 73 , GBC 60 , BRCA 74 , NSCLC 32 and GBM 75 , suggesting that MTDH was defined as a clinical and prognostic biomarker in various cancers, and through detection of MTDH expression, timely diagnosis of cancer patients in early stage may be possible.…”