Chronic pancreatitis and pancreatic cancer demonstrate active epithelial–mesenchymal transition profile, regulated by miR-217-SIRT1 pathway

Abstract

Epithelial-mesenchymal transition (EMT) is supposed to be an inflammation induced response which may take a central role in tumorigenesis. Since recent evidence indicates that microRNAs may be involved in EMT, the present study set out to reveal the miRNA which might regulate the EMT in CP (chronic pancreatitis) and PC (pancreatic cancer) and its potential mechanism. Firstly, we provided evidence that both CP and PC tissues demonstrated active EMT profile. Consistently, miR-217 was obviously down-regulated in CP, PC and TGF-β1 treated PC cells, while negatively correlated to its direct target SIRT1. Moreover, either ectopic expression of miR-217 or inhibition of SIRT1 remarkably induced mesenchymal to epithelial transition (MET) in TGF-β1 treated PC cells. On the contrary, miR-217 inhibitor promoted EMT in PC cells but not in SIRT-knockdown PC cells. Clinical information from a cohort of 54 PC patients demonstrated that down-regulated miR-217 was positively correlated with late tumor stage, lymphatic invasion, vascular infiltration and distant metastasis. These results suggest that the overexpressed TGF-β1 in inflammation triggers the deregulation of the miR-217-SIRT1 pathway and then promotes the EMT process, which might be involved in the tumorigenesis of PC. Additionally, miR-217 may function as a novel target and predictor for PC prevention and therapy.

MicroRNA in pancreatic cancer

“…98 Downregulation of miR-217 upregulates the expression of SIRT1, and SIRT1 mRNA is the direct target of miR-217. 99 Further, upregulation of SIRT1 might facilitate the EMT in patients with chronic pancreatitis and PDAC. 99 CONCLUSION miRNAs that are aberrantly expressed have critical roles in the development and progression of PDAC by influencing cellular functions such as proliferation, apoptosis, metastasis and chemoresistance.…”

“…99 Further, upregulation of SIRT1 might facilitate the EMT in patients with chronic pancreatitis and PDAC. 99 CONCLUSION miRNAs that are aberrantly expressed have critical roles in the development and progression of PDAC by influencing cellular functions such as proliferation, apoptosis, metastasis and chemoresistance. Investigations of the relationship between miRNAs and the development and progression of PDAC provide a better understanding of the molecular mechanisms responsible for the pathogenesis of PDAC, although they raise new questions.…”

Downregulation of miR-199b is associated with distant metastasis in colorectal cancer via activation of SIRT1 and inhibition of CREB/KISS1 signaling

“…In particular, microRNAs (miRNAs), small non-coding RNAs post-transcriptionally regulating gene expression, have been reported to act as a suppressor or promoter in the progression of metastasis in diverse cancer types [5–7]. It has been suggested that miR-199b plays a central role in cancer progression and metastasis, including breast cancer [8], prostate cancer [9], osteosarcoma [10], and medulloblastoma [11].…”

Absent MicroRNAs in Different Tissues of Patients with Acquired Cardiomyopathy

“…Venn diagram showed that 24 absent miRNAs were found to be common among all different tissue types tested. These 24 absent miRNAs were listed in Table 3 [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49]. On the other hand, some miRNAs are only absent in one particular group.…”