Long non-coding RNA ZFAS1 promotes the expression of EPAS1 in gastric cardia adenocarcinoma

Introduction: LncRNA (Long non-coding RNA) ZFAS1 (zinc finger antisense 1) functions as the oncogene in multiple cancers, including gastric cancer. However, its function and underlying mechanism in the GCA (gastric cardia adenocarcinoma), the most aggressive type of gastric cancer, remain unknown. Objective: In the current study, the expression level of LncRNA ZFAS1 was quantified in 762 GCA tissues and the paired adjacent non-tumor tissues. The expression level of LncRNA ZFAS1 was quantified in 762 GCA tissues and the paired adjacent non-tumor tissues, and further confirmed using in vitro cell and animal model based assays. Conclusion: We demonstrated here that the LncRNA ZFAS1 was up-regulated in GCA tissues. Furthermore, the elevated level of ZFAS1 was significantly associated with the GCA metastasis and cancer recurrence. It was also demonstrated to be an independent prognostic indicator of disease-free survival and overall survival for GCA patients. RNA sequencing showed that the up-regulated ZFAS1 was tightly associated with the down-regulated hypoxia inducible factor 1 (HIF1) and up-regulated EPAS1 (Endothelial PAS domain protein 1, also known as HIF2). In vitro studies showed that the ZFAS1 could bind to EPAS1, enhance its abilities to epigenetically silence the HIF1, and promote its own expression in GCA cell lines. In the animal model, codelivering the EPAS1 and the ZFAS1 antisense oligos could significantly boost up their therapeutic effects on tumor growth. Thus, targeting ZFAS1 and EPAS1 might be an alternative therapeutic option in GCA. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of Cairo University.

Automated summary

The study found that LncRNA ZFAS1 is up-regulated in gastric cardia adenocarcinoma (GCA) tissues and closely associated with metastasis and cancer recurrence, serving as an independent prognostic indicator for disease-free survival and overall survival in GCA patients. Targeting ZFAS1 and EPAS1 may provide an alternative therapeutic option for GCA.