Syntenin Regulated by miR-216b Promotes Cancer Progression in Pancreatic Cancer

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.

A novel lysosome-related prognostic signature associated with prognosis and immune infiltration landscape in oral squamous cell carcinoma

“…Crucial to the occurrence and development of melanoma, SDCBP fosters PDAC growth and metastasis by obstructing TrCP-mediated proteasomal degradation [ 22 ]. Elevated levels of SDCBP correlate with an adverse prognosis in pancreatic cancer (PC), stimulate PC cell proliferation, migration, and invasiveness, and trigger epithelial-mesenchymal transition (EMT) through the activation of the PI3K/AKT pathway [ 23 ].…”

SDCBP promotes pancreatic cancer progression by preventing YAP1 from β-TrCP-mediated proteasomal degradation

“…Recently, SDCBP has been identified as a major contributor to several important biological functions in cancers, including tumour invasion, metastasis, proliferation, immune evasion, tumour stemness, exosome loading and angiogenesis 11 15 17 32–34. In pancreatic cancer, the tumour promoting function of SDCBP was evaluated by IHC in 61 pancreatic cancer patients and was further validated using SDCBP-shRNA by Zu et al 18…”

“…SDCBP has been shown to be a major contributor to several important biological functions in solid tumours 10–17. Recent research by Zu et al also reported SDCBP as an oncogene in PDAC progression18; however, the function, mechanism and translation of SDCBP have not been fully explored.…”

The Multifunctional Protein Syntenin-1: Regulator of Exosome Biogenesis, Cellular Function, and Tumor Progression

“…miR-216b is also known to reduce the expression of KRAS, thereby inhibiting the progression of pancreatic cancer and inducing apoptosis [138]. In addition, miR-216b directly targets SDCBP to inhibit its expression, thereby regulating the EMT of pancreatic cancer through the inhibition of the PI3K pathway [129].…”