Rocha Marina Amorim, Cardoso Adauto Lima, Martins Cesar, Mello Maria Luiza S
Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, São Paulo 13083-862, Brazil.
Department of Structural and Functional Biology, Institute of Biosciences at Botucatu, São Paulo State University, Botucatu, São Paulo 18618-689, Brazil.
Oncol Lett. 2024 Jul 11;28(3):432. doi: 10.3892/ol.2024.14563. eCollection 2024 Sep.
p16 and p21 are cyclin-dependent kinase inhibitors involved in cell cycle control, which can function as oncogenes or tumor suppressors, depending on the context of various extracellular and intracellular signals, and cell type. In human papillomavirus-induced cervical cancer, shows oncogenic activity and functions as a diagnostic marker of cervical neoplasia, whereas acts as a tumor suppressor and its downregulation is associated with the progression of malignant transformation. Several histone deacetylase (HDAC) inhibitors promote the positive and negative regulation of a number of genes, including and ; however, the effects of sodium valproate (VPA) on these genes and on the proteins they encode remain uncertain in HeLa cervical cancer cells. In the present study, these effects were investigated in HeLa cells treated with 0.5 or 2 mM VPA for 24 h, using reverse transcription-quantitative PCR, confocal microscopy and western blotting. The results revealed a decrease in the mRNA expression levels of and a tendency for p16 protein abundance to decrease in the presence of 2 mM VPA. By contrast, an increase in the protein expression levels of p21 was detected in the presence of 0.5 and 2 mM VPA. Furthermore, VPA was confirmed to inhibit HDAC activity and induce global hyperacetylation of histone H3. Notably, VPA was shown to suppress , a biomarker gene of cervical carcinoma, and to increase the abundance of the tumor suppressor protein p21, thus contributing to the basic knowledge regarding the antitumorigenic potential of VPA. Exploration of epigenetic changes associated with the promoters of and , such as histone H3 methylation, may provide further information and improve the understanding of these findings.
p16和p21是参与细胞周期调控的细胞周期蛋白依赖性激酶抑制剂，根据各种细胞外和细胞内信号的背景以及细胞类型，它们可以作为癌基因或肿瘤抑制因子发挥作用。在人乳头瘤病毒诱导的宫颈癌中，[此处原文缺失相关基因表述]显示出致癌活性，并作为宫颈肿瘤形成的诊断标志物，而[此处原文缺失相关基因表述]则作为肿瘤抑制因子，其下调与恶性转化的进展相关。几种组蛋白脱乙酰酶（HDAC）抑制剂促进许多基因的正负调控，包括[此处原文缺失相关基因表述]和[此处原文缺失相关基因表述]；然而，丙戊酸钠（VPA）对这些基因及其编码蛋白的影响在HeLa宫颈癌细胞中仍不确定。在本研究中，使用逆转录定量PCR、共聚焦显微镜和蛋白质印迹法，对用0.5或2 mM VPA处理24小时的HeLa细胞中的这些影响进行了研究。结果显示，在存在2 mM VPA的情况下，[此处原文缺失相关基因表述]的mRNA表达水平降低，并且p16蛋白丰度有降低的趋势。相比之下，在存在0.5和2 mM VPA的情况下，检测到p21蛋白表达水平增加。此外，证实VPA抑制HDAC活性并诱导组蛋白H3的整体超乙酰化。值得注意的是，VPA被证明可抑制[此处原文缺失相关基因表述]（一种宫颈癌生物标志物基因），并增加肿瘤抑制蛋白p21的丰度，从而有助于了解VPA的抗肿瘤潜力的基础知识。探索与[此处原文缺失相关基因表述]和[此处原文缺失相关基因表述]启动子相关的表观遗传变化，如组蛋白H3甲基化，可能会提供更多信息并增进对这些发现 的理解。
