2023,
BMC Cancer.
DOI:
10.1186/s12885-023-10543-9
C/EBPβ expression decreases in cervical cancer and leads to tumorigenesis
Haichen Long
, Yangyang Li
, Huijuan Wang
, Bingxuan Guo
, Shuyan Song
, Xiangyi Zhe
, Hongtao Li
, Dongmei Li
, Renfu Shao
, Zemin Pan
Abstract:
Abstract
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.
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2023-06-25 00:06:00
龙海晨:
#paper Haichen Long, Yangyang Li, Huijuan Wang, Bingxuan Guo, Shuyan Song, Xiangyi Zhe, Hongtao Li, Dongmei Li, Renfu Shao, Zemin Pan . C/EBPβ expression decreases in cervical cancer and leads to tumorigenesis. BMC Cancer. 2023 Jan 24;23(1):79. doi: 10.1186/s12885-023-10543-9. PMID: 36694148; PMCID: PMC9872280. 这是我第一次作为第一作者在中科院Top期刊上发的文章，也是2023年发的第二篇文章。是群里分享的第三篇我作为作者的文章。目的是研究C/EBPβ蛋白在宫颈肿瘤发生和发展中的作用。整个过程中，我们采用定量RT-PCR分析临床标本（10例宫颈癌组织标本和10例相应正常宫颈组织标本）中C/EBPβ、miR-661和MTA1 mRNA的表达。应用免疫组织化学方法分析381例临床标本C/EBPβ、80例临床标本Ki67和60例临床标本PCNA蛋白的表达。采用MALDI-TOF MassARRAY分析C/EBPβ基因甲基化（13例宫颈癌症组织和13例相应的正常宫颈组织）。采用CCK-8分析宫颈癌症细胞系的细胞增殖情况。采用蛋白质印迹和免疫组织化学方法检测C/EBPβ蛋白的表达水平，并用定量RT-PCR分析mRNA的表达。采用流式细胞术检测细胞周期分布和细胞凋亡。进行集落形成、Transwell、细胞侵袭和伤口愈合测定以检测细胞迁移和侵袭。
通过实验，我们证明了，C/EBPβ在宫颈癌症组织中降低，C/EBP-β基因在宫颈癌症细胞中的过度表达可以抑制增殖、侵袭和迁移。