MicroRNA-27b functions as a new inhibitor of ovarian cancer-mediated vasculogenic mimicry through suppression of VE-cadherin expression

Abstract

Aggressive cancer cells gain robust tumor vascular mimicry (VM) capability that promotes tumor growth and metastasis. is aberrantly overexpressed in vasculogenic cancer cells and regarded as a master gene of tumor VM. Although microRNAs (miRNAs) play an important role in modulating tumor angiogenesis and cancer metastasis, the miRNA that targets expression in cancer cells to inhibit tumor cell-mediated VM is enigmatic. In this study, we found that miR-27b levels are negatively co-related to expression in ovarian cancer cells and tumor cell-mediated VM, and demonstrated that miR-27b could bind to the 3'-untranslated region (3'UTR) of mRNA. Overexpression of miR-27b in aggressive ovarian cancer cell lines Hey1B and ES2 significantly diminished intracellular expression; convincingly, the inhibitory effect of miR-27b could be reversed by miR-27b specific inhibitor. Intriguingly, miR-27b not only effectively suppressed ovarian cancer cell migration and invasion, but also markedly inhibited formation of ovarian cancer cell-mediated capillary-like structures in vitro and suppressed generation of functional tumor blood vessels in mice. Together, our study suggests that miR-27b functions as a new inhibitor of ovarian cancer cell-mediated VM through suppression of expression, providing a new potential drug candidate for antitumor VM and anti-ovarian cancer therapy.

The regulatory role of microRNAs in angiogenesis‐related diseases

“…Recently, increasing studies demonstrated that the roles of miR‐27b are completely different in different type cancers and vascular diseases 144, 145, 146, 147. A study showed that miR‐27b improves angiogenesis in impaired bone marrow‐derived angiogenic cells (BMAC) in vitro and in vivo in type 2 diabetic mice via directly inhibiting the expression of thrombospondin‐1 (TSP‐1), p66 (shc) and Semaphorin6A (Sema6A), thereby improving the topical cell therapy of diabetic BCACs on wound healing and increasing the wound perfusion and capillary formation 144.…”

“…Overexpression miR‐27b reduces the proliferation, migration and tube formation of HUVECs and decreases angiogenesis in colorectal cancer and gastric cancer via inhibiting the VEGFC/VEGFR2 signalling 147, 148. Moreover, a recent study indicated that miR‐27b effectively represses migration and tube formation of ovarian cancer cells, and angiogenesis in vivo by inhibiting VE‐cadherin 145. In the bladder, prostate and colon tumours, miR‐27b plays anti‐tumour and anti‐angiogenesis roles 147, 149.…”

“…Recently, increasing studies demonstrated that the roles of miR-27b are completely different in different type cancers and vascular diseases. [144][145][146][147] A study showed that miR-27b improves angiogenesis in (PPARc) and IL-10. 146 Coincidently, miR-27b inhibitor inhibits tumour growth and angiogenesis in lung carcinoma.…”

“…147,148 Moreover, a recent study indicated that miR-27b effectively represses migration and tube formation of ovarian cancer cells, and angiogenesis in vivo by inhibiting VE-cadherin. 145 In the bladder, prostate and colon tumours, miR-27b plays anti-tumour and anti-angiogenesis roles. 147,149 These contrary results may be because the effects of miR-27b in different diseases are context-dependent.…”

miRDriver: A Tool to Infer Copy Number Derived miRNA-Gene Networks in Cancer

“…Many studies discovered the affiliation of miRNAs to the cancers driving genes in tumor initiation and progression. For example, miR.125b, miR.145, miR.21 and miR.155 are known to be involved in breast cancer [6] and, miR.27b and miR.181d are known to be involved in ovarian cancer [7][8].…”