Taking advantage of an imperfect match: Inhibition of invasion, metastasis and angiogenesis through miR-205

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Vosgha, H
Salajegheh, A
Lam, A
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Munich, Germany


Background: Epithelial–mesenchymal transition (EMT) is an initiator of tumour progression, implicated in tumour metastasis and increases stemlike properties of cancer cells. There are several transcription factors such as ZEB and SNAIL inducing EMT through repression and loss of epithelial markers like E-cadherin which are involved in malignant transformation mechanisms. In addition to the known role of angiogenesis in generation of new blood vessels, it is also essential for cancer progression. Interestingly, angiogenesis has been found to be linked to EMT-induced cancer cell stemness which is crucial for tumour initiation and metastasis. Anaplastic thyroid carcinoma is classified as the most lethal thyroid cancer due to its aggressive growth, invasive metastases and significant number of recurrences. Cancer stem-like cells (CSCs) are found responsible for therapeutic resistance and metastatic nature of cancer. microRNAs play important roles to modulate gene expression through mRNA degradation/translational repression. miR-205 is considered as a major role player in cancer angiogenesis and EMT process through targeting VEGF-A and ZEB. Material and Methods: In this study, roles of miR-205 in cancer progression, angiogenesis and EMT processes were investigated. Undifferentiated thyroid cancer cells (MB-1 and BHT-101) were permanently transfected by pCMV-MIR-205 expression vector. Expression of VEGF-A and EMT markers, ZEB1, SNAIL and E-Cadherin, were checked using western blotting and enzyme-linked immunosorbent assay (ELISA). Additionally, the aggressiveness and invasiveness of cancer cells were examined by wound healing migration and transwell invasion assays. The ability of human umbilical vein endothelial cells (HUVECs) subjected to pCMV-MIR205 transfected cancer cells to form capillary networks was also evaluated using angiogenesis assay tube formation kit. Results: Western blot analysis showed that VEGF-A, ZEB-1 and SNAIL expression was notably down-regulated in cancer cells after miR-205 vector transfection while E-cadherin up-regulated (P < 0.05). ELISA assay also significantly confirmed a VEGF drop in cancer cell media (P < 0.05). The migratory and invasive ability of stable cell lines have markedly decreased (P < 0.05). Co-culture of HUVECs and transfected cells has significantly blocked endo-tube formation by HUVEC (P < 0.05). Conclusions: Our findings provide important insights into simultaneous regulatory role of miR-205 and its capability in cancer management through affecting several cellular pathways. Because a single miRNA can target several genes at the same, it can add advantage to function of miRNA to control a range of cellular processes leading to tumour formation and metastasis. It might open avenues to use miR-205 as a new therapeutic method for undifferentiated cancers in which angiogenesis and EMT are critical steps. No conflict of interest.

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European Journal of Cancer

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28 EORTC – NCI – AACR Symposium on Molecular Targets and Cancer Therapeutics

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Supplement 1

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Oncology and carcinogenesis

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Life Sciences & Biomedicine


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Vosgha, H; Salajegheh, A; Lam, A, Taking advantage of an imperfect match: Inhibition of invasion, metastasis and angiogenesis through miR-205, European Journal of Cancer, 2016, 69 (Supplement 1), pp. S37-S37