ENTPD5: identification of splicing variants and their impact on cancer survival

Author(s)

de Campos, Rafael Paschoal ^{[1, 2]} ; Wink, Marcia Rosangela ^{[3, 4]} ; Lenz, Guido ^{[1, 2]}

Affiliation

^[1] Univ Fed Rio Grande Sul UFRGS, Ctr Biotecnol, Porto Alegre, RS - Brazil

^[2] Univ Fed Rio Grande Sul UFRGS, Dept Biofis, Rua Bento Goncalves 9500, Predio 43431 Lab 115, BR-91501970 Porto Alegre, RS - Brazil

^[3] Univ Fed Ciencias Saude Porto Alegre UFCSPA, Dept Ciencias Basicas Saude, Porto Alegre, RS - Brazil

^[4] Univ Fed Ciencias Saude Porto Alegre UFCSPA, Lab Biol Celular, Porto Alegre, RS - Brazil

• Document type: Journal article
• Source: PURINERGIC SIGNALLING; v. 17, n. 3, p. 467-480, SEP 2021.
• Web of Science Citations: 1

Abstract

NTPDase5 is a nucleotidase of the endoplasmic reticulum that plays an important role in proteostasis as a regulator of protein N-glycosylation. This enzyme was first identified in hamster as a proto-oncogene activated upon a single nucleotide deletion that causes a frameshift leading to a truncated protein. Truncated NTPDase5 proteins were detected in human samples, but an oncogene was never identified. Searching for transcript variants in the GenBank database and using TCGA data, we discovered that splice variants could originate truncated human NTPDase5 proteins. We identified three main splicing events in the ENTPD5 gene: alternative acceptors, exon skipping, and alternative terminators. The analysis of impact of splicing events in cancers showed that skipping of exon 11-the event that leads to truncated proteins similar in size to the hamster oncogene-does not affect the hazard ratio of most tumors and was, in fact, a protective factor in the only two cancer studies where it was significant. We also identified four main patterns of impact of ENTPD5 in cancer and a potential variant-specific regulation by miR-215. Our findings shed light on a two-decade uncertainty about the origin of truncated NTPDase5 and contribute to the characterization of its impacts in cancer. (AU)

• FAPESP's process: 19/15477-3 - Signalling molecules in the modulation of the transcriptome, metabolic flux and triterpene immunoadjuvant saponins biosynthesis in Quillaja brasiliensis Mart. (Quillajaceae)
• Grantee: Douglas Silva Domingues
• Support Opportunities: Regular Research Grants