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Forkhead box L2 is a target of miR‐133b and plays an important role in the pathogenesis of non‐small cell lung cancer

BACKGROUND: Forkhead box L2 (FOXL2) has been recognized as a transcription factor in the progression of many malignancies, but its role in non‐small cell lung cancer (NSCLC) remains unclear. This research clarified on the role of FOXL2 and the specific molecular mechanism in NSCLC. METHODS: RNA and...

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Autores principales: Li, Juan, Gao, Lirong, Wang, Anqi, Qian, Huiwen, Zhu, Jianjie, Ji, Shundong, Chen, Jun, Liu, Zeyi, Ji, Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10166978/
https://www.ncbi.nlm.nih.gov/pubmed/36846934
http://dx.doi.org/10.1002/cam4.5746
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author Li, Juan
Gao, Lirong
Wang, Anqi
Qian, Huiwen
Zhu, Jianjie
Ji, Shundong
Chen, Jun
Liu, Zeyi
Ji, Cheng
author_facet Li, Juan
Gao, Lirong
Wang, Anqi
Qian, Huiwen
Zhu, Jianjie
Ji, Shundong
Chen, Jun
Liu, Zeyi
Ji, Cheng
author_sort Li, Juan
collection PubMed
description BACKGROUND: Forkhead box L2 (FOXL2) has been recognized as a transcription factor in the progression of many malignancies, but its role in non‐small cell lung cancer (NSCLC) remains unclear. This research clarified on the role of FOXL2 and the specific molecular mechanism in NSCLC. METHODS: RNA and protein levels were detected by quantitative real‐time polymerase chain reaction (qRT–PCR) and western blotting assays. Cell proliferation was examined by cell counting kit‐8 (CCK‐8) and clonogenic assays. Transwell and wound healing assays were used to detect cell invasion and migration. Cell cycle alterations were assessed by flow cytometry. The relationship between FOXL2 and miR‐133b was verified by dual‐luciferase reporter assays. In vivo metastasis was monitored in the tail vein‐injected mice. RESULTS: FOXL2 was upregulated in NSCLC cells and tissues. Downregulation of FOXL2 restrained cell proliferation, migration, and invasion and arrested the cell cycle of NSCLC cells. Moreover, FOXL2 promoted the epithelial–mesenchymal transition (EMT) process of NSCLC cells by inducing the transforming growth factor‐β (TGF‐β)/Smad signaling pathway. miR‐133b directly targeted the 3′‐UTR of FOXL2 and negatively regulated FOXL2 expression. Knockdown of FOXL2 blocked metastasis in vivo. CONCLUSIONS: miR‐133b downregulates FOXL2 by targeting the 3′‐UTR of FOXL2, thereby inhibiting cell proliferation, EMT and metastasis induced by the TGF‐β/Smad signaling pathway in NSCLC. FOXL2 may be a potential molecular target for treating NSCLC.
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spelling pubmed-101669782023-05-10 Forkhead box L2 is a target of miR‐133b and plays an important role in the pathogenesis of non‐small cell lung cancer Li, Juan Gao, Lirong Wang, Anqi Qian, Huiwen Zhu, Jianjie Ji, Shundong Chen, Jun Liu, Zeyi Ji, Cheng Cancer Med RESEARCH ARTICLES BACKGROUND: Forkhead box L2 (FOXL2) has been recognized as a transcription factor in the progression of many malignancies, but its role in non‐small cell lung cancer (NSCLC) remains unclear. This research clarified on the role of FOXL2 and the specific molecular mechanism in NSCLC. METHODS: RNA and protein levels were detected by quantitative real‐time polymerase chain reaction (qRT–PCR) and western blotting assays. Cell proliferation was examined by cell counting kit‐8 (CCK‐8) and clonogenic assays. Transwell and wound healing assays were used to detect cell invasion and migration. Cell cycle alterations were assessed by flow cytometry. The relationship between FOXL2 and miR‐133b was verified by dual‐luciferase reporter assays. In vivo metastasis was monitored in the tail vein‐injected mice. RESULTS: FOXL2 was upregulated in NSCLC cells and tissues. Downregulation of FOXL2 restrained cell proliferation, migration, and invasion and arrested the cell cycle of NSCLC cells. Moreover, FOXL2 promoted the epithelial–mesenchymal transition (EMT) process of NSCLC cells by inducing the transforming growth factor‐β (TGF‐β)/Smad signaling pathway. miR‐133b directly targeted the 3′‐UTR of FOXL2 and negatively regulated FOXL2 expression. Knockdown of FOXL2 blocked metastasis in vivo. CONCLUSIONS: miR‐133b downregulates FOXL2 by targeting the 3′‐UTR of FOXL2, thereby inhibiting cell proliferation, EMT and metastasis induced by the TGF‐β/Smad signaling pathway in NSCLC. FOXL2 may be a potential molecular target for treating NSCLC. John Wiley and Sons Inc. 2023-02-27 /pmc/articles/PMC10166978/ /pubmed/36846934 http://dx.doi.org/10.1002/cam4.5746 Text en © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle RESEARCH ARTICLES
Li, Juan
Gao, Lirong
Wang, Anqi
Qian, Huiwen
Zhu, Jianjie
Ji, Shundong
Chen, Jun
Liu, Zeyi
Ji, Cheng
Forkhead box L2 is a target of miR‐133b and plays an important role in the pathogenesis of non‐small cell lung cancer
title Forkhead box L2 is a target of miR‐133b and plays an important role in the pathogenesis of non‐small cell lung cancer
title_full Forkhead box L2 is a target of miR‐133b and plays an important role in the pathogenesis of non‐small cell lung cancer
title_fullStr Forkhead box L2 is a target of miR‐133b and plays an important role in the pathogenesis of non‐small cell lung cancer
title_full_unstemmed Forkhead box L2 is a target of miR‐133b and plays an important role in the pathogenesis of non‐small cell lung cancer
title_short Forkhead box L2 is a target of miR‐133b and plays an important role in the pathogenesis of non‐small cell lung cancer
title_sort forkhead box l2 is a target of mir‐133b and plays an important role in the pathogenesis of non‐small cell lung cancer
topic RESEARCH ARTICLES
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10166978/
https://www.ncbi.nlm.nih.gov/pubmed/36846934
http://dx.doi.org/10.1002/cam4.5746
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