GSE1 predicts poor survival outcome in gastric cancer patients by SLC7A5 enhancement of tumor growth and metastasis.

Gastric cancer remains a malignancy with poor survival outcome. We herein report that GSE1, a proline-rich protein, possesses a role in the progression of human gastric cancer. The expression of GSE1 was observed to be much higher in human gastric cancer tissues compared with normal gastric tissues, and GSE1 expression correlated positively with lymph node metastasis, histological grade, depth of invasion, and clinical stage in gastric cancer patients. Moreover, GSE1 expression was also associated with decreased post-operative relapse-free survival and overall survival in the cohort. The forced expression of GSE1 in gastric cancer cell lines resulted in increased cell proliferation, increased colony formation, enhanced cell migration, and invasion. Furthermore, forced expression of GSE1 also increased tumor size and enhanced lung metastasis in xenograft models. The depletion of endogenous GSE1 with shRNAs decreased the oncogenicity and invasiveness of gastric cancer cells both in vitro and in vivo In addition, GSE1 was determined to be a direct target of miR-200b and miR-200c. Furthermore, GSE1 positively regulated the downstream gene SLC7A5 (also known as LAT-1), which was scanned and verified from mRNA sequencing. GSE1 therefore possesses an oncogenic role in human gastric cancer, and targeted therapeutic approaches to inhibit GSE1 function in gastric cancer warrant further consideration.

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