Nucleobindin 2 inhibits senescence in gastric carcinoma

Abstract

Background Nucleobindin 2 (NUCB2) is a multifunctional protein that is associated with a variety of biological processes. Here, we focused on the functional role of NUCB2 on progression of gastric carcinoma (GC). Methods NUCB2 expression was investigated in 150 GC cases by immunohistochemistry (IHC), as well as in situ hybridization for detection of the mRNA in 10 cases. GC cell lines were used to determine whether NUCB2 expression was associated with specific cellular phenotypes. Results In GC clinical samples, NUCB2 expression was transcriptionally upregulated when compared to the non-tumoral lesions. High NUCB2 expression was significantly associated with several aggressive clinicopathological factors including deep tumor invasion, lymphovascular invasion, lymph node metastasis, and advanced clinical stages, and was a significant independent prognostic factor for predicting unfavorable progression-free survival in GC patients. In cell lines, NUCB2 knockout inhibited proliferation, susceptibility to apoptosis, and migration capability through an induction of cellular senescence; this was consistent with the significantly higher proliferation and apoptotic indices in NUCB2 IHC-high category as compared to NUCB2 IHC-low GC cases. Conclusions NUCB2-dependent inhibition of senescence in GC leads to aggressive tumor behavior by modulating proliferation, apoptosis, and migration.