TMBIM6-mediated miR-181a expression regulates breast cancer cell migration and invasion via the MAPK/ERK signaling pathway

Shin, Yeokyung; Choi, Hye Yeon; Kwak, Yeonjoo; Yang, Gwang-Mo; Jeong, Yeojin; Jeon, Tak-Il; Seok, Jaekwon; Lee, Eung-Ryoung; Kim, Jung-Hyun; Jeon, Kilsoo; Dayem, Ahmed Abdal; Lim, Kyung Min; Cho, Ssang-Goo

doi:10.7150/jca.81600

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J Cancer 2023; 14(4):554-572. doi:10.7150/jca.81600 This issue Cite

Research Paper

TMBIM6-mediated miR-181a expression regulates breast cancer cell migration and invasion via the MAPK/ERK signaling pathway

Yeokyung Shin^1,2,*, Hye Yeon Choi^1,*, Yeonjoo Kwak¹, Gwang-Mo Yang¹, Yeojin Jeong¹, Tak-Il Jeon¹, Jaekwon Seok¹, Eung-Ryoung Lee¹, Jung-Hyun Kim¹, Kilsoo Jeon¹, Ahmed Abdal Dayem¹, Kyung Min Lim^1,2, Ssang-Goo Cho^1,2,✉

1. Department of Stem Cell & Regenerative Biotechnology and Institute of Advanced Regenerative Science, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea.
2. R&D Team, StemExOne co., ltd. 303, Life Science Bldg, 120, Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
^* These authors contributed equally to the work.

Citation:

Shin Y, Choi HY, Kwak Y, Yang GM, Jeong Y, Jeon TI, Seok J, Lee ER, Kim JH, Jeon K, Dayem AA, Lim KM, Cho SG. TMBIM6-mediated miR-181a expression regulates breast cancer cell migration and invasion via the MAPK/ERK signaling pathway. J Cancer 2023; 14(4):554-572. doi:10.7150/jca.81600. https://www.jcancer.org/v14p0554.htm

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Abstract

Transmembrane Bax Inhibitor Motif-containing 6 (TMBIM6) has been reported to regulate cell death pathways and is overexpressed in several types of cancers. In this study, we investigated whether high expression of TMBIM6 in breast cancer was significantly associated with cancer invasiveness. Knockdown of TMBIM6 reduced proliferation and migration of invasive breast cancer cells through downregulation of the MAPK/ERK signaling pathway. Moreover, we suggested that expression of miR-181a was significantly suppressed upon TMBIM6 knockdown. In contrast, overexpression of TMBIM6 significantly increased cell invasion and migration through up-regulation of mesenchymal markers and matrix metalloproteinase-9 (MMP-9) and enhanced activation of the MAPK/ERK signaling pathway. We also observed that up-regulation of TMBIM6 significantly increased the expression of miR-181a by TMBIM6-mediated pathway. TMBIM6 and miR-181a-mediated ERK activation induced the expression of Snail-1 and Snail-2 in FOSL-1/C-JUN-dependent manner. Overall, our data demonstrated that TMBIM6-induced miR-181a up-regulation plays an important role in the efficient modulation of migration and invasion of breast cancer cells.

Keywords: TMBIM6, miRNA-181a, Breast cancer, MAPK/ ERK signaling pathway, Snail, FOSL-1/c-Jun

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APA

Shin, Y., Choi, H.Y., Kwak, Y., Yang, G.M., Jeong, Y., Jeon, T.I., Seok, J., Lee, E.R., Kim, J.H., Jeon, K., Dayem, A.A., Lim, K.M., Cho, S.G. (2023). TMBIM6-mediated miR-181a expression regulates breast cancer cell migration and invasion via the MAPK/ERK signaling pathway. Journal of Cancer, 14(4), 554-572. https://doi.org/10.7150/jca.81600.

ACS

Shin, Y.; Choi, H.Y.; Kwak, Y.; Yang, G.M.; Jeong, Y.; Jeon, T.I.; Seok, J.; Lee, E.R.; Kim, J.H.; Jeon, K.; Dayem, A.A.; Lim, K.M.; Cho, S.G. TMBIM6-mediated miR-181a expression regulates breast cancer cell migration and invasion via the MAPK/ERK signaling pathway. J. Cancer 2023, 14 (4), 554-572. DOI: 10.7150/jca.81600.

NLM

CSE

Shin Y, Choi HY, Kwak Y, Yang GM, Jeong Y, Jeon TI, Seok J, Lee ER, Kim JH, Jeon K, Dayem AA, Lim KM, Cho SG. 2023. TMBIM6-mediated miR-181a expression regulates breast cancer cell migration and invasion via the MAPK/ERK signaling pathway. J Cancer. 14(4):554-572.

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