Sorting nexin-1 is a candidate tumor suppressor and potential prognostic marker in gastric cancer

Abstract

Sorting nexin-1 (SNX1) is an important functional protein in cell endocytosis, efflux, protein sorting, cell signal transduction, etc; however, the expression, the role and clinical relevance of SNX1 have not been investigated in gastric cancer (GC). In this study, we first performed a bioinformatics investigation using the data obtained from The Cancer Genome Atlas (TCGA) database. The result showed that SNX1 mRNA levels were significantly lower in GC tissues than in paracancerous tissues. In a study of 150 cases of GC, including 60 cases with paired paracancerous and cancer tissues and 90 cases with detailed follow-up information, SNX1 expression was analyzed by immunohistochemistry. Our study on paired paracancerous and cancer tissues showed that SNX1 protein expression remarkably decreased in GC tissues (50/60, 83.33%). A study on 90 patients with detailed follow-up information showed that tumors with higher SNX1 protein level were correlated with better clinicopathologic stages (p = 0.0285), nodal status (p = 0.0286), smaller tumor sizes (p = 0.0294) and a better survival rate in patients with GC (p = 0.0245). Univariate analysis of the 90 patients with GC showed that low-level SNX1 was significantly correlated with decreased overall survival of GC patients (p = 0.008), and associated with a relatively higher cumulative hazard of death. Exogenous expression of SNX1 inhibited the growth, migration, invasion and promoted the apoptosis and enhanced the sensitivity of GC cells to the chemotherapeutic drug 5-Fluorouracil (5-Fu) in vitro, while knockdown of SNX1 by short hairpin RNA (shRNA) significantly promoted the growth, migration, invasion and reduced the apoptosis and the sensitivity of GC cells to 5-Fu. SNX1 also showed to influence the levels of epithelial-mesenchymal transition markers including Vimentin, Snail, and E-cadherin in GC cells in vitro. Taken together, we propose here that SNX1 serves as a tumor suppressor and prognostic marker that reduces tumor cell malignancy for GC.

lncRNA TMEM51-AS1 and RUSC1-AS1 function as ceRNAs for induction of laryngeal squamous cell carcinoma and prediction of prognosis

“…miR-106b was reported to promote the proliferation and invasion of LSCC cells by targeting RUNX3 (Ying et al, 2013), while induce cell cycle G0/G1 arrest by inhibiting tumor suppressor RB (Cai, Wang & Bao, 2011). Although no study revealed the roles of SNX21 in cancer, its family genes, such as SNX1 (Zhan et al, 2018), SNX5 (Jitsukawa et al, 2017) and SNX9 (Bendris et al, 2016) were suggested to be tumor suppressor related. Therefore, SNX21 may be theoretically downregulated in LSCC by miR-106b.…”

Sorting nexins: A novel promising therapy target for cancerous/neoplastic diseases

“…Therefore, SNX1 may be involved in protein sorting from early endosomes to lysosomes. SNX1 may affect the lysosome degradation of some proteins, including the ubiquity- (Zhan et al, 2018). SNX1 suppresses the growth, migration, and invasion, and also promotes the activation of apoptosis, thereby promoting the sensitivity of GC cells to the chemotherapeutic drug 5-Fluorouracil (5-Fu).…”

Promotion of esophageal adenocarcinoma metastasis via Wnt/ß‐catenin signal pathway by sorting nexins 3

“…22 Several studies showed that SNX1 is associated with the development and metastasis of some tumors, including lung cancer and colon cancer. [23][24][25] SNX3 could also cause EGFR aggregation in the early endosome and prevent EGFR transport to lysosome for degradation in human epidermoid cancer cell. 13 Thus, EGFR signaling pathway might be another possible target of SNX3 in tumorigenesis of EAC and worth further study.…”

“…SNX1 could suppress EGFR membrane recycling and activate EGFR/PI3K/AKT signaling pathway in lung cancer cells 22 . Several studies showed that SNX1 is associated with the development and metastasis of some tumors, including lung cancer and colon cancer 23–25 . SNX3 could also cause EGFR aggregation in the early endosome and prevent EGFR transport to lysosome for degradation in human epidermoid cancer cell 13 .…”