J Cancer 2021; 12(16):4849-4861. doi:10.7150/jca.55719

Research Paper

MRPS17 promotes invasion and metastasis through PI3K/AKT signal pathway and could be potential prognostic marker for gastric cancer

Wenjie Zhou1,2*, Jun Ouyang1,2*, Junqing Li1,2*, Fangjie Liu4, Tailai An1, Lvjia Cheng1,2, Zi Chong Kuo1, Changhua Zhang1✉, Yulong He1,2✉

1. Digestive Disease Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Zhenyuan Road 628, Guangming District, Shenzhen 518000, Guangdong, China.
2. Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Zhongshan 2nd Road 58, Yuexiu District, Guangzhou 510080, Guangdong, China.
3. Department of Pathology, The Seventh Affiliated Hospital, Sun Yat-sen University, Zhenyuan Road 628, Guangming District, Shenzhen 518000, Guangdong, China.
4. Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan 2nd Road 58, Yuexiu District, Guangzhou 510080, Guangdong, China.
5. Scientific Research Centre, The Seventh Affiliated Hospital, Sun Yat-sen University, 628 Zhenyuan Road 628, Guangming District, Shenzhen 518000, Guangdong, China.
*These authors contributed equally to this work.

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Citation:
Zhou W, Ouyang J, Li J, Liu F, An T, Cheng L, Kuo ZC, Zhang C, He Y. MRPS17 promotes invasion and metastasis through PI3K/AKT signal pathway and could be potential prognostic marker for gastric cancer. J Cancer 2021; 12(16):4849-4861. doi:10.7150/jca.55719. Available from https://www.jcancer.org/v12p4849.htm

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Abstract

In this study, the molecular mechanisms through which Mitochondrial Ribosomal Protein S17 (MRPS17) contributes to gastric cancer (GC) and its prognostic significance in GC have been explored. As a protein encoding gene, MRPS17 encodes a 28s proteins belonging the ribosomal protein S17P family. The specific roles and molecular mechanisms of MRPS17 in cancers remain ambiguous. It was revealed by analyzing data from TCGA and GEO that elevated expression of MRPS17 was significantly associated with invasion of GC and poor survival of GC patients. Then through univariate and multivariate Cox regression analyses it was demonstrated that MRPS17 an independent prognostic factor for GC patients (P<0.001). It was demonstrated by differentially expressed gene analysis and functional enrichment analysis that MPRS17 is related to PI3K/AKT pathway and Cell adhesion molecules (CAMs), while its function is mediated by collagen-containing extracellular matrix and receptor ligand/regulator activity. Then it was proven by in-vitro experiments that knocking down of MRPS17 gene in AGS and SGC7901 cells would significantly inhibit proliferation and invasion capability of these cells. Furthermore, it was revealed by cell immunofluorescence assay that as a ribosomalprotein, MRPS17 was mainly distributed in the cytoplasmic surface of cell membrane. Additionally, activation of PI3K/AKT pathway is responsible for malignant progression of glioma that was promoted by MRPS17.

In conclusion, it was revealed in the present study that MRPS17 promoted invasion and metastasis of GC and potential molecular mechanisms through which it exerted its influences on GC were explored, suggesting its potential as a novel prognostic biomarker for GC.

Keywords: gastric cancer, TCGA, PI3K/AKT signaling pathway, invasion and migration