Abstract
Pancreatic cancer (PC) remains a primary cause of cancer‐related deaths worldwide. Existing literature has highlighted the oncogenic role of microRNA‐27a (miR‐27a) in multiple cancers. Hence, the current study aimed to clarify the potential therapeutic role of PC cell–derived exosomal miR‐27a in human microvascular endothelial cell (HMVEC) angiogenesis in PC. Initially, differentially expressed genes (DEGs) and miRs related to PC were identified by microarray analysis. Microarray analysis provided data predicting the interaction between miR‐27a and BTG2 in PC, which was further verified by the elevation or depletion of miR‐27a. Next, the expression of miR‐27a and BTG2 in the PC tissues was quantified. HMVECs were exposed to exosomes derived from PC cell line PANC‐1 to investigate the effects associated with PC cell–derived exosomes carrying miR‐27a on HMVEC proliferation, invasion and angiogenesis. Finally, the effect of miR‐27a on tumorigenesis and microvessel density (MVD) was analysed after xenograft tumour inoculation in nude mice. Our results revealed that miR‐27a was highly expressed, while BTG2 was poorly expressed in both PC tissues and cell lines. miR‐27a targeted BTG2. Moreover, miR‐27a silencing inhibited PC cell proliferation and invasion, and promoted apoptosis through the elevation of BTG2. The in vitro assays revealed that PC cell–derived exosomes carrying miR‐27a stimulated HMVEC proliferation, invasion and angiogenesis, while this effect was reversed in the HMVECs cultured with medium containing GW4869‐treated PANC‐1 cells. Furthermore, in vivo experiment revealed that miR‐27a knockdown suppressed tumorigenesis and MVD. Taken together, cell‐derived exosomes carrying miR‐27a promotes HMVEC angiogenesis via BTG2 in PC.
Highlights
Pancreatic cancer (PC) ranks as the seventh leading cause of can‐ cer‐related death worldwide, accounting for approximately 4% of all cancer cases with about 330,000 deaths per year.[1]
Both miRs and miR exosomes have been speculated to be promising PC therapeutic tar‐ gets through the protein transfer‐induced target cell reprogramme and binding‐triggered signal transduction.[8] miRs are a group of short non‐coding RNA molecules with the length of 18‐22 nucle‐ otides, which regulate genes associated with cell apoptosis, differ‐ entiation and neoplastic transformation.[9]
The present study investigated the effect of PC cell–derived exosomal miR‐27a on PC through the regulation of B‐cell translocation gene 2 (BTG2)
Summary
Pancreatic cancer (PC) ranks as the seventh leading cause of can‐ cer‐related death worldwide, accounting for approximately 4% of all cancer cases with about 330,000 deaths per year.[1].
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