Abstract
Pancreatic cancer is one of the most deadly cancers with a poor prognosis. Though studies have implicated the roles of microRNAs in pancreatic cancer progression, little is known about the role of miR-613 in pancreatic cancer. In the present study, the expression of miR-613 was down-regulated in pancreatic cancer tissues and cancer cell lines. Down-regulation of miR-613 was positively correlated with tumor differentiation, advanced TNM stage, nodal metastasis and shorter overall survival in patients with pancreatic cancer. Overexpression of miR-613 suppressed cell proliferation, invasion and migration, and induced cell apoptosis and cell cycle arrest at G0/G1 phase in pancreatic cancer cells. Bioinformatics analysis, luciferase reporter assay and rescue experiments showed that notch3 was a direct target of miR-613. MiR-613 was inversely correlated with notch3 expression in pancreatic cancer tissues. The long non-coding RNA, HOX transcript antisense RNA (HOTAIR) was up-regulated in both pancreatic cancer tissues and cancer cell lines, and HOTAIR suppressed the expression of miR-613 via functioning as a competing endogenous RNA. In vivo studies showed that stable overexpression of miR-613 or knock-down of HOTAIR suppressed tumor growth and also reduced the expression of notch3. In conclusion, these results suggest that HOTAIR functions as a competing endogenous RNA to regulate notch3 expression via sponging miR-613 in pancreatic cancer.
Highlights
Pancreatic cancer is one of the most deadly cancers with a poor prognosis, and the overall 5-year survival rate is less than 5% due to advanced stage disease at initial diagnosis, frequent recurrence and the lack of effective therapies [1]
Down-regulation of miR-613 was positively correlated with tumor differentiation, advanced TNM stage, nodal metastasis and shorter overall survival in patients with pancreatic cancer
The expression level of miR-613 in pancreatic cancer tissues was classified into low expression of miR-613 and high expression of miR613 based on the median values of miR-613 expression in p
Summary
Pancreatic cancer is one of the most deadly cancers with a poor prognosis, and the overall 5-year survival rate is less than 5% due to advanced stage disease at initial diagnosis, frequent recurrence and the lack of effective therapies [1]. Even with the advancement in medicine, pancreatic cancer is still resistant to current treatment regimens [3]. In this regard, it is important for us to understand the molecular mechanisms underlying pancreatic cancer progression. Our study has shown that the lncRNA, HOX transcript antisense RNA (HOTAIR) regulates the expression of miR-663b via the histone modification, which results in the regulation of pancreatic cancer progression [14]. HOTAIR was found to control the expression of Rab22a by sponging miR-373 in ovarian cancer [15]; Liu et al, showed that HOTAIR functions as a competing endogenous RNA to regulated human epidermal growth factor receptor 2 (HER2) expression by sponging miR-331-3p in gastric cancer [16]. Whether HOTAIR functions as a competing endogenous RNA to regulate pancreatic cancer progression is largely unknown
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