Mitofusin-2 modulates the epithelial to mesenchymal transition in thyroid cancer progression

Abstract Here, we investigated the potential roles of Mitofusin-2 (MFN2) in thyroid cancer progression. MFN2 regulates mitochondrial fusion/division in cells and plays an important role in various aspects of cell metabolism. MFN2 might involve in cell cycle regulation, apoptosis, and differentiation...

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Autores principales:	Mi-Hyeon You, Min Ji Jeon, Seong ryeong Kim, Woo Kyung Lee, Sheue-yann Cheng, Goo Jang, Tae Yong Kim, Won Bae Kim, Young Kee Shong, Won Gu Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cf36640e2d7e4d22bb715fc4453357df
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spelling	oai:doaj.org-article:cf36640e2d7e4d22bb715fc4453357df2021-12-02T14:09:01ZMitofusin-2 modulates the epithelial to mesenchymal transition in thyroid cancer progression10.1038/s41598-021-81469-02045-2322https://doaj.org/article/cf36640e2d7e4d22bb715fc4453357df2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81469-0https://doaj.org/toc/2045-2322Abstract Here, we investigated the potential roles of Mitofusin-2 (MFN2) in thyroid cancer progression. MFN2 regulates mitochondrial fusion/division in cells and plays an important role in various aspects of cell metabolism. MFN2 might involve in cell cycle regulation, apoptosis, and differentiation, and it might play a role as a tumor suppressor in carcinogenesis. We evaluated the prognostic impacts of MFN2 expression in thyroid cancer by analyzing TCGA data. In vitro and in vivo, MFN2 was knocked out using CRISPR/Cas9 or siRNA, and MFN2 was stably overexpressed in two thyroid cancer cell lines (Cal62 and HTH83). TCGA analysis revealed that MFN2 expression was lower in thyroid cancer than in normal tissues and significantly associated with a degree of differentiation, RAS mutations, and less lymph node metastasis. MFN2 expression was significantly correlated with cell adhesion molecules and epithelial to mesenchymal transition (EMT) in a gene-set enrichment assay. MFN2 knock-out (KO) in Cal62 and HTH83 cells using CRISPR/Cas9 or siRNA significantly promoted cell migration and invasion in vitro. The same trends were observed in MFN2 KO mouse embryonic fibroblasts (MEFs) compared to those in the controls (MFN2 WT MEFs). Conversely, MFN2 overexpression in cancer cell lines greatly inhibited cell migration and invasion. However, there was no difference in colony formation and proliferation in Cal62 and HTH83 cells after modulating MFN2, although there were significant differences between MFN KO and WT MEFs. EMT-associated protein expression was induced after MFN2 KO in both cancer cell lines. The mechanistic results suggest that MFN2 might modulate EMT through inducing the AKT signaling pathway. EMT-associated changes in protein expression were also confirmed by modulating MFN2 in xenograft tumors. Thus, MFN2 acts as a tumor suppressor in thyroid cancer progression and metastasis by modulating EMT.Mi-Hyeon YouMin Ji JeonSeong ryeong KimWoo Kyung LeeSheue-yann ChengGoo JangTae Yong KimWon Bae KimYoung Kee ShongWon Gu KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mi-Hyeon You Min Ji Jeon Seong ryeong Kim Woo Kyung Lee Sheue-yann Cheng Goo Jang Tae Yong Kim Won Bae Kim Young Kee Shong Won Gu Kim Mitofusin-2 modulates the epithelial to mesenchymal transition in thyroid cancer progression
description	Abstract Here, we investigated the potential roles of Mitofusin-2 (MFN2) in thyroid cancer progression. MFN2 regulates mitochondrial fusion/division in cells and plays an important role in various aspects of cell metabolism. MFN2 might involve in cell cycle regulation, apoptosis, and differentiation, and it might play a role as a tumor suppressor in carcinogenesis. We evaluated the prognostic impacts of MFN2 expression in thyroid cancer by analyzing TCGA data. In vitro and in vivo, MFN2 was knocked out using CRISPR/Cas9 or siRNA, and MFN2 was stably overexpressed in two thyroid cancer cell lines (Cal62 and HTH83). TCGA analysis revealed that MFN2 expression was lower in thyroid cancer than in normal tissues and significantly associated with a degree of differentiation, RAS mutations, and less lymph node metastasis. MFN2 expression was significantly correlated with cell adhesion molecules and epithelial to mesenchymal transition (EMT) in a gene-set enrichment assay. MFN2 knock-out (KO) in Cal62 and HTH83 cells using CRISPR/Cas9 or siRNA significantly promoted cell migration and invasion in vitro. The same trends were observed in MFN2 KO mouse embryonic fibroblasts (MEFs) compared to those in the controls (MFN2 WT MEFs). Conversely, MFN2 overexpression in cancer cell lines greatly inhibited cell migration and invasion. However, there was no difference in colony formation and proliferation in Cal62 and HTH83 cells after modulating MFN2, although there were significant differences between MFN KO and WT MEFs. EMT-associated protein expression was induced after MFN2 KO in both cancer cell lines. The mechanistic results suggest that MFN2 might modulate EMT through inducing the AKT signaling pathway. EMT-associated changes in protein expression were also confirmed by modulating MFN2 in xenograft tumors. Thus, MFN2 acts as a tumor suppressor in thyroid cancer progression and metastasis by modulating EMT.
format	article
author	Mi-Hyeon You Min Ji Jeon Seong ryeong Kim Woo Kyung Lee Sheue-yann Cheng Goo Jang Tae Yong Kim Won Bae Kim Young Kee Shong Won Gu Kim
author_facet	Mi-Hyeon You Min Ji Jeon Seong ryeong Kim Woo Kyung Lee Sheue-yann Cheng Goo Jang Tae Yong Kim Won Bae Kim Young Kee Shong Won Gu Kim
author_sort	Mi-Hyeon You
title	Mitofusin-2 modulates the epithelial to mesenchymal transition in thyroid cancer progression
title_short	Mitofusin-2 modulates the epithelial to mesenchymal transition in thyroid cancer progression
title_full	Mitofusin-2 modulates the epithelial to mesenchymal transition in thyroid cancer progression
title_fullStr	Mitofusin-2 modulates the epithelial to mesenchymal transition in thyroid cancer progression
title_full_unstemmed	Mitofusin-2 modulates the epithelial to mesenchymal transition in thyroid cancer progression
title_sort	mitofusin-2 modulates the epithelial to mesenchymal transition in thyroid cancer progression
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/cf36640e2d7e4d22bb715fc4453357df
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Mitofusin-2 modulates the epithelial to mesenchymal transition in thyroid cancer progression

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