Abstract
Dysregulation of microRNAs (miRNAs) exerts key roles in the development of pancreatic cancer (PCa). miR-26a is reportedly a tumor suppressor in cancers. However, whether miR-26a modulates PCa progression is poorly understood. Here, we found that miR-26a was down-regulated in PCa. Overexpressed miR-26a suppressed PCa cell proliferation, colony formation, and tumor stem cell properties. Mechanically, the transcription factor E2F7 is a downstream target of miR-26a. miR-26a decreased E2F7 expression through binding to the 3’-untranslated region (UTR) of E2F7. Decreased miR-26a in PCa tissues was inversely correlated with E2F7. The inhibitory effects of miR-26a in PCa were reversed by E2F7 overexpression. Consistently, the knockout of E2F7 further significantly inhibited the growth of PCa cells combined with miR-26a overexpression. Further study revealed that E2F7 bound the promoter of vascular endothelial growth factor A (VEGFA), a key factor in angiogenesis, and transcriptionally activated the expression of VEGFA. miR-26a overexpression attenuated the effects of E2F7 on VEGFA promotion. Our results uncovered the novel function of miR-26a/E2F7/VEGFA in PCa, making miR-26a a possible target for PCa treatment.
Highlights
Pancreatic cancer (PCa) is a well-known fatal aggressive tumor with a poor prognosis [1,2,3]
Considering the down-regulation of miR-26a in PCa, we further investigated the biological roles of miR-26a via gainof-function experiments
To determine whether miR-26a affected PCa cell growth via modulation of the stemness, we examined the expression of OCT4, CD133, Nanog, and SOX2, the stem-cell-like markers. miR-26a overexpression reduced the expression of these four stem-cell markers in PCa cells when compared to the control group (Fig. 2F), which suggests inhibited stem cell properties of PCa cells with overexpressed miR-26a. miR-26a inhibits the malignant behaviors of PCa
Summary
Pancreatic cancer (PCa) is a well-known fatal aggressive tumor with a poor prognosis [1,2,3]. It is the seventh leading cause of cancer-related death worldwide. Surgery remains the only potentially curative treatment for patients with early pancreatic cancer [4,5,6]. MiRNAs affect the development of PCa by targeting key factors associated with cancer progression [18,19,20,21,22]. Deregulated miRNAs show correlation with the diagnosis, prognosis and response to current therapies of pancreatic cancer patients [23].
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