Abstract
Outcomes for patients with pancreatic cancer (PC) are poor; therefore, there is an urgent need to identify novel therapeutic targets involved in the progression of PC. We previously identified 161 differentially expressed proteins (DEPs) in PC. Syntenin (SDCBP) was identified as a survival-related protein through integrated, survival, and Cox analyses. High expression of SDCBP was associated with a poor prognosis in PC tissue and promoted the proliferation, migration, and invasion of PC cells, and induced epithelial–mesenchymal transition (EMT) via the PI3K/AKT pathway. Additionally, we elucidated the regulatory mechanism underlying these roles of SDCBP at the post-transcriptional level. microRNAs (miRNAs) of SDCBP were predicted using bioinformatics. Low levels of miR-216b expression were confirmed in PC tissues and were negatively correlated with SDCBP expression. miR-216b was found to directly regulate SDCBP expression through luciferase reporter assays. Furthermore, agomiR-216b restrained PC proliferation, migration, invasion, and EMT via the PI3K/AKT pathway, whereas antagomiR-216b facilitated this process. Notably, the knockout of SDCBP counteracted the effect of antagomiR-216b in PC, which suggested that miR-216b and SDCBP represent molecular targets underlying PC progression and EMT. Finally, the results were validated in in vivo studies. These findings indicated that low expression of miR-216b and the oncogene SDCBP contributes to PC migration, invasion, and EMT, and that they have potential as future therapeutic targets for patients with PC.
Highlights
Pancreatic cancer (PC) is associated with a high mortality rate, high recurrence rate, and low cure rate, ranking eleventh in morbidity and sixth in mortality among all cancers [1, 2]
Our findings indicated that the miR-216b/ SDCBP axis promotes PC progression and induced epithelial–mesenchymal transition (EMT) via the PI3K/AKT pathway, which may represent potential future therapeutic targets
Considering that SDCBP was identified as a direct target of miR-216b, we validated the roles of miR-216b in EMT and the PI3K/AKT pathway
Summary
Pancreatic cancer (PC) is associated with a high mortality rate, high recurrence rate, and low cure rate, ranking eleventh in morbidity and sixth in mortality among all cancers [1, 2]. Based on GLOBOCAN 2018 estimates, there were approximately 459,000 new cases of PC and 432,000 deaths each year [3]. The high mortality and recurrence of PC make the disease difficult to treat. Approximately 80%–85% of patients are diagnosed with unresectable or metastatic disease, which is associated with poor overall survival (OS) [4]. MiR-216b Targeted Syntenin in Cancer Progression with PC remain unsatisfactory, with only 10% surviving 5 years [5, 6]. There is an urgent need to identify novel therapeutic targets involved in the progression of PC
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