Department of Biochemistry and Molecular Biology, School of Medicine, Xinjiang Endemic and Ethnic Disease and Education Ministry Key Laboratory, Shihezi University, Shihezi, 832002, Xinjiang, China.
Department of Clinical Laboratory, First Affiliated Hospital of School of Medicine, Shihezi University, Shihezi, 832000, Xinjiang, China.
BMC Cancer. 2023 Jan 24;23(1):79. doi: 10.1186/s12885-023-10543-9.
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.
To explore the role of the C/EBPβ protein in cervical tumorigenesis and progression.
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.
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.
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.
宫颈癌目前估计是全世界女性中第四常见的癌症，也是一些世界上最贫穷国家癌症相关死亡的主要原因。C/EBPβ 具有肿瘤抑制作用，因为它是癌基因诱导衰老所必需的。然而，C/EBPβ 也具有致癌作用。C/EBPβ 在宫颈癌中作为肿瘤抑制因子或癌蛋白的具体作用尚不清楚。
探讨 C/EBPβ 蛋白在宫颈癌发生发展中的作用。
采用定量 RT-PCR 分析临床样本（10 例宫颈癌组织样本和 10 例相应正常宫颈组织样本）中 C/EBPβ（15 例宫颈癌组织样本和 15 例相应正常宫颈组织样本）、miR-661 和 MTA1mRNA 的表达。采用免疫组织化学法分析 C/EBPβ（381 例临床样本）、Ki67（80 例临床样本）和 PCNA（60 例临床样本）蛋白的表达。采用 MALDI-TOF MassARRAY 分析 C/EBPβ 基因甲基化（13 例宫颈癌组织和 13 例相应正常宫颈组织）。采用 CCK-8 分析宫颈癌细胞系的细胞增殖。通过 Western blot 和免疫组化检测 C/EBPβ 蛋白表达水平，并通过定量 RT-PCR 分析检测 mRNA 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、细胞侵袭和划痕愈合试验，以检测细胞迁移和侵袭。
与宫颈炎组织相比，宫颈癌组织中 C/EBPβ 蛋白表达明显降低（P<0.01）。宫颈癌组织中 Ki67 蛋白和 PCNA 蛋白的表达水平明显高于宫颈炎组织。与正常宫颈组织相比，宫颈癌组织中 C/EBPβ 基因启动子 CpG12、13、14 和 CpG19 的甲基化率显著升高（P<0.05）。此外，在宫颈癌细胞中过表达 C/EBPβ，过表达 C/EBPβ 基因可抑制细胞增殖、迁移、侵袭，使细胞停滞在 S 期，并促进细胞凋亡。
我们已经证明，C/EBPβ 在宫颈癌组织中减少，宫颈癌细胞中 C/EBPβ 基因的过表达可抑制增殖、侵袭和迁移。
