NME2 Is a Master Suppressor of Apoptosis in Gastric Cancer Cells via Transcriptional Regulation of miR-100 and Other Survival Factors.

Tumorigenesis is a result of uncontrollable cell proliferation which is regulated by a variety of complex factors including miRNAs. The initiation and progression of cancer are always accompanied by the dysregulation of miRNAs. However, the underlying mechanism of miRNA dysregulation in cancers is still largely unknown. Herein we found that miR-100 was inordinately upregulated in the sera of patients with gastric cancer, indicating that miR-100 might emerge as a biomarker for the clinical diagnosis of cancer. The abnormal expression of miR-100 in gastric cancer cells was mediated by a novel transcription factor NME2 (NME/NM23 nucleoside diphosphate kinase 2). Further data revealed that the transcription factor NME2 could promote the transcriptions of antiapoptotic genes including miRNA (i.e., miR-100) and protein-encoding genes (RIPK1, STARD5, and LIMS1) through interacting with RNA polymerase II and RNA polymerase II-associated protein 2 to mediate the phosphorylation of RNA polymerase II C-terminal domain at the 5th serine, leading to the suppression of apoptosis of gastric cancer cells both in vitro and in vivo. In this context, our study revealed that the transcription factor NME2 is a master suppressor for apoptosis of gastric cancer cells. IMPLICATIONS: Our study contributed novel insights into the mechanism involved in the expression regulation of apoptosis-associated genes and provided a potential biomarker of gastric cancer. ©2019 American Association for Cancer Research.