Different splicing isoforms of ERCC1 affect the expression of its overlapping genes CD3EAP and PPP1R13L, and indicate a potential application in non-small cell lung cancer treatment

Abstract

Numerous genes are arranged in complex overlapping and interlaced patterns, and such arrangements potentially contribute to the regulation of gene expression. Previous studies have demonstrated that a region in chromosome 19q13.2-3 encompassing the overlapping genes excision repair cross-complementation group 1 (ERCC1), CD3e molecule associated protein (CD3EAP) and protein phosphatase 1 regulatory subunit 13 like (PPP1R13L) was found to be associated with the risk and prognosis of non-small cell lung cancer (NSCLC). The present study confirmed the hypothesis that there are co-expression patterns among these overlapping genes. The suggestive bioinformatic evidence of The Cancer Genome Atlas was verified by quantitative polymerase chain reaction (qPCR) analysis of NSCLC tissue samples. In addition, a cisplatin-induced DNA damage cell model was assessed by microarray analysis, qPCR and 3' rapid amplification of cDNA ends (3'RACE) to verify and quantify the expression levels of co-expressed alternative splicing isoforms in the NSCLC tissues, as well as in cancer A549 and normal 16HBE cells. The expression of CD3EAP exon 1 was demonstrated to be significantly associated with PPP1R13L exon 1, while CD3EAP exon 3 was significantly associated with ERCC1 exon 11 in normal and NSCLC tissues. It was observed that short transcripts of ERCC1, CD3EAP and PPP1R13L are co-expressed in A549 cells and full-length transcripts are co-expressed in 16HBE cells. Furthermore, a novel transcriptional regulation pattern was described based on the positional associations of overlapping genes. The region encompassing the overlapping genes ERCC1, CD3EAP and PPP1R13L may be involved in linking the upstream and downstream genes, while the different splicing isoforms of ERCC1 affect the expression of its overlapping genes, suggesting potential application in cisplatin resistance in NSCLC treatment.

Rs3212986 polymorphism, a possible biomarker to predict smoking‐related lung cancer, alters DNA repair capacity via regulating ERCC1 expression

“…In another previous study, we confirmed that co‐expression patterns were consisted in overlapping genes as ERCC1 , CD3EAP, and PPP1R13L. Particularly, there was a significant association between CD3EAP exon 3 and ERCC1 exon 11, while CD3EAP exon 1 and PPP1R13L exon 1 . The potential influence of CD3EAP expression was in response to the regulation of genetic networks known to be associated with DRC and lung cancer risk.…”

AC138128.1 an Intronic lncRNA originating from ERCC1 Implies a Potential Application in Lung Cancer Treatment

“…And then their correlation at the mRNA level in cancer tissues but not in para-cancer tissues was found. Some reports and our previous study confirmed that numerous alternative splicing events occur in ERCC1 , which means different spliceosomes of ERCC1 expressed differently in cancer and para-cancer tissues 22, 33, 34. The difference of the association between AC138128.1 and ERCC1 expression in cancer and para-cancer tissues may be due to the changes in the alternative splicing isoform of ERCC1 expression in cancer and para-cancer.…”

“…All detection service was performed by OE Biotech's (Shanghai, China). The method of data standardization has been described previously 22. The upstream and downstream 100k nts of ERCC1 gene is from 45876341 to 46078414 in chromosome 19 (GRCh37).…”

A prognostic model for predicting recurrence-free survival in hepatocellular carcinoma patients

“…In other scholars' prognostic analysis of HCC, CD3EAP is also a predictor, suggesting that CD3EAP is an important predictor of HCC prognosis, but the function of CD3EAP is not completely clear (22). The function of GAS2L3 is still unknown; it may be involved in mediating the absorption and clearance of prostaglandins, but it has not reported in liver cancer (13).…”