LincRNA-uc002yug.2 involves in alternative splicing of RUNX1 and serves as a predictor for esophageal cancer and prognosis

Abstract

Long intergenic noncoding RNAs (lincRNAs) have critical regulatory roles in cancer biology; however, the contributions of lincRNAs to esophageal squamous cell carcinoma (ESCC) have been infrequently explored. The aim of this study was to explore the contribution of lincRNAs, located at ESCC susceptibility loci identified by genome-wide association studies, to the risk and prognosis of ESCC. The associations between lincRNAs and the risk and prognosis of ESCC were analyzed in 358 diagnosed patients from eastern China, and the findings were validated in 326 additional patients from southern China. Functional relevance of lincRNAs was further examined by biochemical assays. We found that lincRNA-uc002yug.2 was commonly overexpressed in ESCC compared with paired peritumoral tissue in eastern and southern Chinese populations. The expression levels of lincRNA-uc002yug.2 in ESCC might be a prognostic factor for survival. Moreover, lincRNA-uc002yug.2 promoted a combination of RUNX1 and alternative splicing (AS) factors in the nucleus to produce more RUNX1a, the short isoform and inhibitor of RUNX1, and reduce CEBPα (CCAAT/enhancer-binding protein-α) gene expression, thereby promoting ESCC progression. These results indicated that lincRNA-uc002yug.2 might involve in AS of RUNX1/AML1 and serve as a predictor for esophageal cancer and prognosis.

Overexpression of RUNX1 short isoform has an important role in the development of myelodysplastic/myeloproliferative neoplasms

“…The possibility that other mechanisms are involved also needs to be considered. 18 Pathogenic functions of RUNX1a have been reported in mouse models. However, this is not clear in patients with myeloid neoplasms.…”

The noncoding function of NELFA mRNA promotes the development of oesophageal squamous cell carcinoma by regulating the Rad17‐RFC2‐5 complex

“…Previous studies have shown that lncRNAs play crucial roles in the occurrence and development of ESCC (Wu et al , ; Yao et al , ; Zhang et al , ). In our study, the most notable finding was that the noncoding function of NELFA mRNA plays an important role in oesophageal cancer progression.…”

Non-coding RNAs: new biomarkers and therapeutic targets for esophageal cancer

“…lncRNA uc002yug.2 was overexpressed in esophageal cancer, which could exert oncogenic effect by overexpressing RUNX1a and reducing CEBPα gene expression. These data suggest that lincRNA-uc002yug.2 level could be a prognostic factor for the esophageal cancer patients’ survival [58]. …”