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CircWHSC1 Promotes Breast Cancer Progression by Regulating the FASN/AMPK/mTOR Axis Through Sponging miR-195-5p

Numerous studies reveal that circular RNAs (circRNAs) affect cancer progression. CircWHSC1 is a novel circRNA that accelerates ovarian cancer progression. Nevertheless, the function of circWHSC1 in regulating breast cancer (BC) is elusive. Here, quantitative reverse transcription-polymerase chain re...

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Autores principales: Chen, Qian, Yang, Zhen, Ding, Hongjian, Li, Huaqing, Wang, Weiyu, Pan, Zhiyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766753/
https://www.ncbi.nlm.nih.gov/pubmed/35070947
http://dx.doi.org/10.3389/fonc.2021.649242
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author Chen, Qian
Yang, Zhen
Ding, Hongjian
Li, Huaqing
Wang, Weiyu
Pan, Zhiyu
author_facet Chen, Qian
Yang, Zhen
Ding, Hongjian
Li, Huaqing
Wang, Weiyu
Pan, Zhiyu
author_sort Chen, Qian
collection PubMed
description Numerous studies reveal that circular RNAs (circRNAs) affect cancer progression. CircWHSC1 is a novel circRNA that accelerates ovarian cancer progression. Nevertheless, the function of circWHSC1 in regulating breast cancer (BC) is elusive. Here, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was carried out to detect the profiles of circWHSC1 and miR-195-5p in BC tissues and corresponding non-tumor tissues. Gain- and loss-of-function assays were implemented both in vivo and ex vivo to verify the significance of circWHSC1 in BC development. BC cell proliferation was estimated by the cell counting kit-8 (CCK-8) and BrdU assays. Transwell assay was implemented to test BC cell migration and invasion. The protein levels of FASN, AMPK and mTOR were determined by Western blot. Moreover, immunohistochemistry was performed to examine Ki67 and FASN expression. As shown by the result, circWHSC1 was up-regulated in BC tissues versus adjacent non-tumor tissues. circWHSC1 overexpression was correlated with higher tumor stages, lymphatic metastasis and worse survival of BC patients. Functionally, overexpressing circWHSC1 amplified proliferation, migration and invasion of BC cell lines and boosted xenograft tumor growth in nude mice. Bioinformatics uncovered that circWHSC1 functioned as a competitive endogenous RNA by sponging miR-195-5p, which was further corroborated by the dual-luciferase reporter assay and RNA immunoprecipitation. miR-195-5p delayed BC progression, which was dampened by circWHSC1 up-regulation. Fatty acid synthase (FASN) was affirmed as a direct target of miR-195-5p. miR-195-5p overexpression curbed FASN expression and activated its downstream AMPK pathway. Inhibition of FASN or activation of the AMPK pathway reversed circWHSC1-mediated oncogenic effects. Collectively, CircWHSC1 acted as an oncogene to expedite BC evolvement by modulating the miR-195-5p/FASN/AMPK/mTOR pathway.
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spelling pubmed-87667532022-01-20 CircWHSC1 Promotes Breast Cancer Progression by Regulating the FASN/AMPK/mTOR Axis Through Sponging miR-195-5p Chen, Qian Yang, Zhen Ding, Hongjian Li, Huaqing Wang, Weiyu Pan, Zhiyu Front Oncol Oncology Numerous studies reveal that circular RNAs (circRNAs) affect cancer progression. CircWHSC1 is a novel circRNA that accelerates ovarian cancer progression. Nevertheless, the function of circWHSC1 in regulating breast cancer (BC) is elusive. Here, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was carried out to detect the profiles of circWHSC1 and miR-195-5p in BC tissues and corresponding non-tumor tissues. Gain- and loss-of-function assays were implemented both in vivo and ex vivo to verify the significance of circWHSC1 in BC development. BC cell proliferation was estimated by the cell counting kit-8 (CCK-8) and BrdU assays. Transwell assay was implemented to test BC cell migration and invasion. The protein levels of FASN, AMPK and mTOR were determined by Western blot. Moreover, immunohistochemistry was performed to examine Ki67 and FASN expression. As shown by the result, circWHSC1 was up-regulated in BC tissues versus adjacent non-tumor tissues. circWHSC1 overexpression was correlated with higher tumor stages, lymphatic metastasis and worse survival of BC patients. Functionally, overexpressing circWHSC1 amplified proliferation, migration and invasion of BC cell lines and boosted xenograft tumor growth in nude mice. Bioinformatics uncovered that circWHSC1 functioned as a competitive endogenous RNA by sponging miR-195-5p, which was further corroborated by the dual-luciferase reporter assay and RNA immunoprecipitation. miR-195-5p delayed BC progression, which was dampened by circWHSC1 up-regulation. Fatty acid synthase (FASN) was affirmed as a direct target of miR-195-5p. miR-195-5p overexpression curbed FASN expression and activated its downstream AMPK pathway. Inhibition of FASN or activation of the AMPK pathway reversed circWHSC1-mediated oncogenic effects. Collectively, CircWHSC1 acted as an oncogene to expedite BC evolvement by modulating the miR-195-5p/FASN/AMPK/mTOR pathway. Frontiers Media S.A. 2022-01-05 /pmc/articles/PMC8766753/ /pubmed/35070947 http://dx.doi.org/10.3389/fonc.2021.649242 Text en Copyright © 2022 Chen, Yang, Ding, Li, Wang and Pan https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Chen, Qian
Yang, Zhen
Ding, Hongjian
Li, Huaqing
Wang, Weiyu
Pan, Zhiyu
CircWHSC1 Promotes Breast Cancer Progression by Regulating the FASN/AMPK/mTOR Axis Through Sponging miR-195-5p
title CircWHSC1 Promotes Breast Cancer Progression by Regulating the FASN/AMPK/mTOR Axis Through Sponging miR-195-5p
title_full CircWHSC1 Promotes Breast Cancer Progression by Regulating the FASN/AMPK/mTOR Axis Through Sponging miR-195-5p
title_fullStr CircWHSC1 Promotes Breast Cancer Progression by Regulating the FASN/AMPK/mTOR Axis Through Sponging miR-195-5p
title_full_unstemmed CircWHSC1 Promotes Breast Cancer Progression by Regulating the FASN/AMPK/mTOR Axis Through Sponging miR-195-5p
title_short CircWHSC1 Promotes Breast Cancer Progression by Regulating the FASN/AMPK/mTOR Axis Through Sponging miR-195-5p
title_sort circwhsc1 promotes breast cancer progression by regulating the fasn/ampk/mtor axis through sponging mir-195-5p
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766753/
https://www.ncbi.nlm.nih.gov/pubmed/35070947
http://dx.doi.org/10.3389/fonc.2021.649242
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