Nucleoporin 37 promotes the cell proliferation, migration, and invasion of gastric cancer through activating the PI3K/AKT/mTOR signaling pathway.

Abstract

Gastric cancer is a kind of malignant tumor in the world. Emerging studies have proved the regulatory role of nucleoporin 37 in the development of several malignant tumors. However, the potential effect of NUP37 in gastric cancer is still unclear. In this study, we searched for the Cancer Genome Atlas analysis to explore the potential correlation between NUP37 and gastric cancer. Then, we analyzed NUP37 expression in gastric cancer tissues and cell lines. After constructing a NUP37-silenced model in NCI-N87 cells and a NUP37-overexpressed model in MKN45 cells, we evaluated the role of NUP37 in cell proliferation, migration, and invasion as well as its underlying mechanism. TCGA analysis showed that NUP37 expression was highly expressed in stomach adenocarcinoma, which showed a lower survival rate than normal samples. Moreover, NUP37 was found to be highly expressed in gastric cancer tissues and cell lines. Functionally, NUP37 deficiency promoted gastric cancer cell apoptosis and inhibited cell proliferation, migration, and invasion, whereas NUP37 overexpression exhibited the opposite results. Mechanically, upregulation of NUP37 activated the PI3K/AKT/mTOR signaling pathway. Furthermore, the rescue assay exhibited that the mTOR inhibitor rapamycin significantly reversed the promoting effect of NUP37 in cell proliferation, migration, and invasion. In conclusion, our study identified that NUP37 promoted malignant behavior of gastric cancer cells including invasion, proliferation, and migration through activating the PI3K and its downregulated signaling pathway, indicating that NUP37 might become a novel prognostic target for further gastric cancer therapy.

• Authors: Jishui Zhang, Wenhao Lv, Yagang Liu, Weihua Fu, Baosheng Chen, Qiutong Ma, Xin Gao, Xiuxia Cui
• Journal: In vitro cellular & developmental biology. Animal (In Vitro Cell Dev Biol Anim) Vol. 57 Issue 10 Pg. 987-997 (Dec 2021) ISSN: 1543-706X [Electronic] Germany
• PMID: 34888748 (Publication Type: Journal Article)
• Copyright: © 2021. The Society for In Vitro Biology.

Chemical References

• MTOR protein, human
• Nuclear Pore Complex Proteins
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases
• NUP37 protein, human

Topics

• Humans
• Adenocarcinoma (genetics, metabolism, pathology)
• Apoptosis (genetics)
• Cell Line, Tumor
• Cell Movement (physiology)
• Cell Proliferation (physiology)
• Gene Expression Regulation, Neoplastic
• Nuclear Pore Complex Proteins (genetics, metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction
• Stomach Neoplasms (genetics, metabolism, pathology)
• TOR Serine-Threonine Kinases (metabolism)