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Volume 12
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10.3390/genes12010045
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Article

MiR-146a Regulates Migration and Invasion by Targeting NRP2 in Circulating-Tumor Cell Mimicking Suspension Cells

by
Yeojin Do
1,
Jin Gu Cho
1,
Ji Young Park
1,
Sumin Oh
1,
Doyeon Park
1,
Kyung Hyun Yoo
1,2,
Myeong-Sok Lee
1,2,
Byung Su Kwon
3,*,
Jongmin Kim
1,2,* and
Young Yang
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
Department of Obstetrics and Gynecology, Kyung Hee University Medical Center, 23, Seoul 02447, Korea
*
Authors to whom correspondence should be addressed.
Genes 2021, 12(1), 45; https://doi.org/10.3390/genes12010045
Submission received: 30 November 2020 / Revised: 28 December 2020 / Accepted: 28 December 2020 / Published: 30 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

Cancer metastasis is the primary cause of cancer-related death and metastatic cancer has circulating-tumor cells (CTCs), which circulate in the bloodstream before invading other organs. Thus, understanding the precise role of CTCs may provide new insights into the metastasis process and reduce cancer mortality. However, the molecular characteristics of CTCs are not well understood due to a lack of number of CTCs. Therefore, suspension cells were generated from MDA-MB-468 cells to mimic CTCs, and we investigate the microRNA (miRNA)-dependent molecular networks and their role in suspension cells. Here, we present an integrated analysis of mRNA and miRNA sequencing data for suspension cell lines, through comparison with adherent cells. Among the differentially regulated miRNA–mRNAs axes, we focus on the miR-146a-Neuropilin2 (NRP2) axis, which is known to influence tumor aggressiveness. We show that miR-146a directly regulates NRP2 expression and inhibits Semaphorin3C (SEMA3C) signaling. Functional studies reveal that miR-146a represses SEMA3C-induced invasion and proliferation by targeting NRP2. Finally, high-NRP2 is shown to be associated with poor outcomes in breast cancer patients. This study identifies the key role of the miR-146a–NRP2 signaling axis that is critical for the regulation of migration and invasion in CTC-mimicking cells.
Keywords: circulating-tumor cell; metastasis; MicroRNA; neuropilin2 (NRP2); semaphorin3C (SEMA3C); suspension cell circulating-tumor cell; metastasis; MicroRNA; neuropilin2 (NRP2); semaphorin3C (SEMA3C); suspension cell

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MDPI and ACS Style

Do, Y.; Cho, J.G.; Park, J.Y.; Oh, S.; Park, D.; Yoo, K.H.; Lee, M.-S.; Kwon, B.S.; Kim, J.; Yang, Y. MiR-146a Regulates Migration and Invasion by Targeting NRP2 in Circulating-Tumor Cell Mimicking Suspension Cells. Genes 2021, 12, 45. https://doi.org/10.3390/genes12010045

AMA Style

Do Y, Cho JG, Park JY, Oh S, Park D, Yoo KH, Lee M-S, Kwon BS, Kim J, Yang Y. MiR-146a Regulates Migration and Invasion by Targeting NRP2 in Circulating-Tumor Cell Mimicking Suspension Cells. Genes. 2021; 12(1):45. https://doi.org/10.3390/genes12010045

Chicago/Turabian Style

Do, Yeojin, Jin Gu Cho, Ji Young Park, Sumin Oh, Doyeon Park, Kyung Hyun Yoo, Myeong-Sok Lee, Byung Su Kwon, Jongmin Kim, and Young Yang. 2021. "MiR-146a Regulates Migration and Invasion by Targeting NRP2 in Circulating-Tumor Cell Mimicking Suspension Cells" Genes 12, no. 1: 45. https://doi.org/10.3390/genes12010045

APA Style

Do, Y., Cho, J. G., Park, J. Y., Oh, S., Park, D., Yoo, K. H., Lee, M.-S., Kwon, B. S., Kim, J., & Yang, Y. (2021). MiR-146a Regulates Migration and Invasion by Targeting NRP2 in Circulating-Tumor Cell Mimicking Suspension Cells. Genes, 12(1), 45. https://doi.org/10.3390/genes12010045

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