MicroRNA 34a–AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells

Lim, Dansaem; Cho, Jin Gu; Yun, Eunsik; Lee, Aram; Ryu, Hong-Yeoul; Lee, Young Joo; Yoon, Sukjoon; Chang, Woochul; Lee, Myeong-Sok; Kwon, Byung Su; Kim, Jongmin

doi:10.3390/genes12010009

Open AccessArticle

MicroRNA 34a–AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells

by

Dansaem Lim

^1,†,

Jin Gu Cho

^1,†,

Eunsik Yun

^1,†,

Aram Lee

^1,2,

Hong-Yeoul Ryu

³,

Young Joo Lee

⁴

,

Sukjoon Yoon

^1,2,

Woochul Chang

⁵

,

Myeong-Sok Lee

^1,2,

Byung Su Kwon

^4,*

and

Jongmin Kim

^1,2,*

¹

Division of Biological Sciences, Sookmyung Women’s University, Seoul 04310, Korea

²

Research Institute for Women’s Health, Sookmyung Women’s University, Seoul 04310, Korea

³

School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, College of National Sciences, Kyungpook National University, Daegu 41566, Korea

⁴

Department of Obstetrics and Gynecology, Kyung Hee University Medical Center, 23, Seoul 02447, Korea

⁵

Department of Biology Education, College of Education, Pusan National University, Busan 46241, Korea

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Genes 2021, 12(1), 9; https://doi.org/10.3390/genes12010009

Submission received: 13 November 2020 / Revised: 11 December 2020 / Accepted: 18 December 2020 / Published: 23 December 2020

(This article belongs to the Special Issue Non-coding RNAs: Variety of Roles and Applications in Human Diseases)

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Abstract

Targeting the tumor vasculature is an attractive strategy for cancer treatment. However, the tumor vasculature is heterogeneous, and the mechanisms involved in the neovascularization of tumors are highly complex. Vasculogenic mimicry (VM) refers to the formation of vessel-like structures by tumor cells, which can contribute to tumor neovascularization, and is closely related to metastasis and a poor prognosis. Here, we report a novel function of AXL receptor tyrosine kinase (AXL) in the regulation of VM formation in breast cancer cells. MDA-MB-231 cells exhibited VM formation on Matrigel cultures, whereas MCF-7 cells did not. Moreover, AXL expression was positively correlated with VM formation. Pharmacological inhibition or AXL knockdown strongly suppressed VM formation in MDA-MB-231 cells, whereas the overexpression of AXL in MCF-7 cells promoted VM formation. In addition, AXL knockdown regulated epithelial–mesenchymal transition (EMT) features, increasing cell invasion and migration in MDA-MB-231 cells. Finally, the overexpression of microRNA-34a (miR-34a), which is a well-described EMT-inhibiting miRNA and targets AXL, inhibited VM formation, migration, and invasion in MDA-MB 231 cells. These results identify a miR-34a–AXL axis that is critical for the regulation of VM formation and may serve as a therapeutic target to inhibit tumor neovascularization.

Keywords: breast cancer; vasculogenic mimicry; epithelial–mesenchymal transition; AXL; miR-34a

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MDPI and ACS Style

Lim, D.; Cho, J.G.; Yun, E.; Lee, A.; Ryu, H.-Y.; Lee, Y.J.; Yoon, S.; Chang, W.; Lee, M.-S.; Kwon, B.S.; et al. MicroRNA 34a–AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells. Genes 2021, 12, 9. https://doi.org/10.3390/genes12010009

AMA Style

Lim D, Cho JG, Yun E, Lee A, Ryu H-Y, Lee YJ, Yoon S, Chang W, Lee M-S, Kwon BS, et al. MicroRNA 34a–AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells. Genes. 2021; 12(1):9. https://doi.org/10.3390/genes12010009

Chicago/Turabian Style

Lim, Dansaem, Jin Gu Cho, Eunsik Yun, Aram Lee, Hong-Yeoul Ryu, Young Joo Lee, Sukjoon Yoon, Woochul Chang, Myeong-Sok Lee, Byung Su Kwon, and et al. 2021. "MicroRNA 34a–AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells" Genes 12, no. 1: 9. https://doi.org/10.3390/genes12010009

APA Style

Lim, D., Cho, J. G., Yun, E., Lee, A., Ryu, H.-Y., Lee, Y. J., Yoon, S., Chang, W., Lee, M.-S., Kwon, B. S., & Kim, J. (2021). MicroRNA 34a–AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells. Genes, 12(1), 9. https://doi.org/10.3390/genes12010009

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MicroRNA 34a–AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells

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