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

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.

• Authors: Feng Sun, Mengchao Yu, Jing Yu, Zhijian Liu, Xinyan Zhou, Yanqing Liu, Xiaolong Ge, Haidong Gao, Mei Li, Xiaohong Jiang, Song Liu, Xi Chen, Wenxian Guan
• Journal: Cell death & disease (Cell Death Dis) Vol. 9 Issue 5 Pg. 522 (05 01 2018) ISSN: 2041-4889 [Electronic] England
• PMID: 29743567 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3' Untranslated Regions
• MIRN338 microRNA, human
• MicroRNAs
• Neoplasm Proteins
• RNA, Neoplasm
• PTPN1 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 1

Topics

• 3' Untranslated Regions
• Animals
• Cell Line, Tumor
• Cell Movement (genetics)
• Genes, Tumor Suppressor
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Neoplasm Proteins (genetics, metabolism)
• Protein Tyrosine Phosphatase, Non-Receptor Type 1 (genetics, metabolism)
• RNA, Neoplasm (genetics, metabolism)
• Stomach Neoplasms (genetics, metabolism, pathology)