MiR-338-3p functions as a tumor suppressor in gastric cancer by targeting PTP1B

Feng Sun,Haidong Gao,Jing Yu,Mengchao Yu,Zhijian Liu,Xiaohong Jiang,Yanqing Liu,Wenxian Guan,Song Liu,Xinyan Zhou,Xi Chen,Mei Li,Xiaolong Ge

doi:10.1038/s41419-018-0611-0

Abstract

Gastric cancer (GC) is one of the most common malignant tumors and peritoneal metastasis is the primary cause for advanced GC’s mortality. Protein-tyrosine phosphatase 1B (PTP1B) functions as an oncogene and involves in carcinogenesis and cancer dissemination. However, the function and regulation of PTP1B in GC remain poorly understood. In this study, we found that PTP1B was upregulated in GC tissues and overexpression of PTP1B in vitro promoted cell migration and prevented apoptosis. Then, we predicted that PTP1B was a target of miR-338-3p and we revealed an inverse correlation between miR-338-3p levels and PTP1B protein levels in GC tissues. Next, we verified that PTP1B was inhibited by miR-338-3p via direct targeting to its 3′-untranslated regions. Moreover, overexpression of miR-338-3p in vitro attenuated GC cell migration and promoted apoptosis, and these effects could be partially reversed by reintroduction of PTP1B. Finally, we established an orthotopic xenograft model and a peritoneal dissemination model of GC to demonstrate that miR-338-3p restrained tumor growth and dissemination in vivo by targeting PTP1B. Taken together, our results highlight that PTP1B is an oncogene and is negatively regulated by miR-338-3p in GC, which may provide new insights into novel molecular therapeutic targets for GC.

Highlights

There exist almost one million new cases of gastric cancer (GC) every year worldwide and half of these occur in Eastern Asia, China in particular
Protein-tyrosine phosphatase 1B (PTP1B) was upregulated and it functioned as an oncogene in Gastric cancer (GC)
We found that PTP1B protein levels were remarkably higher in GC tissues compared with those of the noncancerous counterparts (Fig. 1a, b)

Summary

Introduction

There exist almost one million new cases of gastric cancer (GC) every year worldwide and half of these occur in Eastern Asia, China in particular. The incidence of GC has declined over the years, it remains the fifth most common cancer and the third leading cause of cancer-related death in the world[1]. The poor prognosis of GC is mainly attributed to tumor metastasis and recurrence. Cancer metastasis is a multi-step process facilitated by several cancer-related molecular factors[4]. Take peritoneal dissemination of GC as an example. Formation of metastasis involves detachment from the primary tumor, migration, and attachment to mesothelial cells, invasion into subperitoneal tissue, and proliferation with angiogenesis[5]. A large number of studies have been carried out to elucidate the molecular mechanisms involved in each step, the complicated underlying mechanisms remain unclear. Protein-tyrosine phosphatase 1B (PTP1B), encoded by the PTPN1 gene in Official journal of the Cell Death Differentiation Association

Methods

Results

Conclusion