Pancreatic cancer cell–derived exosomal microRNA‐27a promotes angiogenesis of human microvascular endothelial cells in pancreatic cancer via BTG2

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.

The involvement of exosomes in the diagnosis and treatment of pancreatic cancer

“…Besides, accumulating shreds of evidence proved that exosomes play an essential role in pancreatic cancer angiogenesis [51]. Shang et al reported that PC cellderived exosomal microRNA-27a significantly stimulated the angiogenesis of HMVEC in pancreatic cancer through BTG2 [52]. In conclusion, exosomes affect pancreatic cancer progression by regulating essential features such as angiogenesis, EMT, cell proliferation, and metastasis.…”

SNHG12 inhibits oxygen‑glucose deprivation‑induced neuronal apoptosis via the miR‑181a‑5p/NEGR1 axis

“…Putative miR-181a-5p binding sites in SNHG12 and binding sites in the 3′-untranslated region (UTR) of NEGR1 to miR-181a-5p were predicted using StarBase ( , v2.0; September 2013 release) and TargetScan ( , v7.2; March 2018 release) ( 26 ). Sequence fragments SHNG12-wild-type (WT) and SHNG12-mutant (MT) and WT and MT 3′-UTR fragments of NEGR1 containing putative miR-181a-5p binding sites were cloned into pmirGLO dual-luciferase reporter vectors (Promega Corporation) and confirmed by sequencing using Illumina MiSeq MiSeqdxDNA (Illumina, Inc.) according to the manufacturer's protocol.…”

The potential roles of exosomes in pancreatic cancer initiation and metastasis

“…It has been shown that miR-27a is overexpressed in cancer tissues from PaCa patients as well as PaCa cell lines [ 147 ]. PaCa-derived exosomes containing miR-27a can induce proliferation, invasion and angiogenesis in human microvascular endothelial cells (HMVECs) by suppressing B-cell translocation gene 2 (BTG2), which promotes PaCa cell survival and growth [ 121 ]. In contrast, in vivo studies using PaCa animal models have demonstrated miR-339-5p can inhibit cell invasion and migration by down-regulating the expression the zinc finger protein ZNF689.…”