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C/EBPβ expression decreases in cervical cancer and leads to tumorigenesis

BACKGROUND: Cervical cancer is currently estimated to be the fourth most common cancer among women worldwide and the leading cause of cancer-related deaths in some of the world’s poorest countries. C/EBPβ has tumor suppressor effects because it is necessary for oncogene-induced senescence. However,...

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Autores principales: Long, Haichen, Li, Yangyang, Wang, Huijuan, Guo, Bingxuan, Song, Shuyan, Zhe, Xiangyi, Li, Hongtao, Li, Dongmei, Shao, Renfu, Pan, Zemin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9872280/
https://www.ncbi.nlm.nih.gov/pubmed/36694148
http://dx.doi.org/10.1186/s12885-023-10543-9
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author Long, Haichen
Li, Yangyang
Wang, Huijuan
Guo, Bingxuan
Song, Shuyan
Zhe, Xiangyi
Li, Hongtao
Li, Dongmei
Shao, Renfu
Pan, Zemin
author_facet Long, Haichen
Li, Yangyang
Wang, Huijuan
Guo, Bingxuan
Song, Shuyan
Zhe, Xiangyi
Li, Hongtao
Li, Dongmei
Shao, Renfu
Pan, Zemin
author_sort Long, Haichen
collection PubMed
description BACKGROUND: Cervical cancer is currently estimated to be the fourth most common cancer among women worldwide and the leading cause of cancer-related deaths in some of the world’s poorest countries. C/EBPβ has tumor suppressor effects because it is necessary for oncogene-induced senescence. However, C/EBPβ also has an oncogenic role. The specific role of C/EBPβ in cervical cancer as a tumor suppressor or oncoprotein is unclear. OBJECTIVE: To explore the role of the C/EBPβ protein in cervical tumorigenesis and progression. METHODS: Quantitative RT-PCR was used to analyze C/EBPβ (15 cervical cancer tissue samples and 15 corresponding normal cervical tissue samples), miR-661, and MTA1 mRNA expression in clinical samples (10 cervical cancer tissue samples and 10 corresponding normal cervical tissue samples). Immunohistochemistry was used to analyze C/EBPβ (381 clinical samples), Ki67 (80 clinical samples) and PCNA ( 60 clinical samples) protein expression. MALDI-TOF MassARRAY was used to analyze C/EBPβ gene methylation (13 cervical cancer tissues and 13 corresponding normal cervical tissues). Cell proliferation was analyzed by CCK-8 in cervical cancer cell lines. Western blotting and immunohistochemistry were performed to detect C/EBPβ protein expression levels, and mRNA expression was analyzed by quantitative RT-PCR analysis. Flow cytometry was performed to measure cell cycle distribution and cell apoptosis. Colony formation, Transwell, cell invasion, and wound healing assays were performed to detect cell migration and invasion. RESULTS: C/EBPβ protein expression was significantly reduced in cervical cancer tissues compared with cervicitis tissues (P < 0.01). Ki67 protein and PCNA protein expression levels were significantly higher in cervical cancer tissues compared with cervicitis tissues. The rate of C/EBPβ gene promoter methylation of CpG12, 13, 14 and CpG19 in cervical cancer tissues was significantly increased compared with normal cervical tissue (P < 0.05). In addition, C/EBPβ was overexpressed in cervical cancer cells and this overexpression inhibited cell proliferation, migration, invasion, arrested cells in S phase, and promoted apoptosis. CONCLUSIONS: We have demonstrated that C/EBPβ decreased in cervical cancer tissues and overexpression of the C/EBPβ gene in cervical cancer cells could inhibit proliferation, invasion and migration. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10543-9.
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spelling pubmed-98722802023-01-25 C/EBPβ expression decreases in cervical cancer and leads to tumorigenesis Long, Haichen Li, Yangyang Wang, Huijuan Guo, Bingxuan Song, Shuyan Zhe, Xiangyi Li, Hongtao Li, Dongmei Shao, Renfu Pan, Zemin BMC Cancer Research BACKGROUND: Cervical cancer is currently estimated to be the fourth most common cancer among women worldwide and the leading cause of cancer-related deaths in some of the world’s poorest countries. C/EBPβ has tumor suppressor effects because it is necessary for oncogene-induced senescence. However, C/EBPβ also has an oncogenic role. The specific role of C/EBPβ in cervical cancer as a tumor suppressor or oncoprotein is unclear. OBJECTIVE: To explore the role of the C/EBPβ protein in cervical tumorigenesis and progression. METHODS: Quantitative RT-PCR was used to analyze C/EBPβ (15 cervical cancer tissue samples and 15 corresponding normal cervical tissue samples), miR-661, and MTA1 mRNA expression in clinical samples (10 cervical cancer tissue samples and 10 corresponding normal cervical tissue samples). Immunohistochemistry was used to analyze C/EBPβ (381 clinical samples), Ki67 (80 clinical samples) and PCNA ( 60 clinical samples) protein expression. MALDI-TOF MassARRAY was used to analyze C/EBPβ gene methylation (13 cervical cancer tissues and 13 corresponding normal cervical tissues). Cell proliferation was analyzed by CCK-8 in cervical cancer cell lines. Western blotting and immunohistochemistry were performed to detect C/EBPβ protein expression levels, and mRNA expression was analyzed by quantitative RT-PCR analysis. Flow cytometry was performed to measure cell cycle distribution and cell apoptosis. Colony formation, Transwell, cell invasion, and wound healing assays were performed to detect cell migration and invasion. RESULTS: C/EBPβ protein expression was significantly reduced in cervical cancer tissues compared with cervicitis tissues (P < 0.01). Ki67 protein and PCNA protein expression levels were significantly higher in cervical cancer tissues compared with cervicitis tissues. The rate of C/EBPβ gene promoter methylation of CpG12, 13, 14 and CpG19 in cervical cancer tissues was significantly increased compared with normal cervical tissue (P < 0.05). In addition, C/EBPβ was overexpressed in cervical cancer cells and this overexpression inhibited cell proliferation, migration, invasion, arrested cells in S phase, and promoted apoptosis. CONCLUSIONS: We have demonstrated that C/EBPβ decreased in cervical cancer tissues and overexpression of the C/EBPβ gene in cervical cancer cells could inhibit proliferation, invasion and migration. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10543-9. BioMed Central 2023-01-24 /pmc/articles/PMC9872280/ /pubmed/36694148 http://dx.doi.org/10.1186/s12885-023-10543-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Long, Haichen
Li, Yangyang
Wang, Huijuan
Guo, Bingxuan
Song, Shuyan
Zhe, Xiangyi
Li, Hongtao
Li, Dongmei
Shao, Renfu
Pan, Zemin
C/EBPβ expression decreases in cervical cancer and leads to tumorigenesis
title C/EBPβ expression decreases in cervical cancer and leads to tumorigenesis
title_full C/EBPβ expression decreases in cervical cancer and leads to tumorigenesis
title_fullStr C/EBPβ expression decreases in cervical cancer and leads to tumorigenesis
title_full_unstemmed C/EBPβ expression decreases in cervical cancer and leads to tumorigenesis
title_short C/EBPβ expression decreases in cervical cancer and leads to tumorigenesis
title_sort c/ebpβ expression decreases in cervical cancer and leads to tumorigenesis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9872280/
https://www.ncbi.nlm.nih.gov/pubmed/36694148
http://dx.doi.org/10.1186/s12885-023-10543-9
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