NUPR1 participates in YAP-mediate gastric cancer malignancy and drug resistance via AKT and p21 activation.

Abstract

To assess nuclear protein 1 (NUPR1) level in human gastric cancer (GC) cells, explore the effects of NUPR1 on GC progression, and investigate the possible regulatory mechanism. Immunohistochemistry (IHC), Immunoblot and quantitative PCR assays were conducted to detect the NUPR1 level in human GC tissues and corresponding normal tissues. Also, NUPR1 expression level correlates with clinical features of GC patients. 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT), transwell assays, Immunoblot assays, and flow cytometry (FCM) assays were used to evaluate the effects of NUPR1 on the proliferation, invasion, epithelial-mesenchymal transformation (EMT) and apoptosis of GC cells in vitro. Immunoblot assays were performed to detect the potential mechanism in NUPR1-mediated drug resistance. We found the expression of NUPR1 was upregulated in human gastric cancer tissues and correlated with the clinical features including tumour size, tumour stage and, lymph node metastasis. We further noticed that the depletion of NUPR1 inhibited the invasion and EMT of gastric cancer cells and stimulated the apoptosis. In doxorubicin-resistant gastric cancer cells, yes-associated protein (YAP) activation was up-regulated, and YAP could regulate the expression of NUPR1 to affect drug-resistance. We further provided the evidence that overexpression of NUPR1 reversed the effect of YAP knockdown on cell malignancy and drug resistance via regulating AKT and p21 pathway. Our findings indicated the involvement of NUPR1 in the progression of gastric cancer and elucidated its molecular mechanism in regulating drug resistance.