Nucleic Acids and Proteins Laboratory, Faculty of Chemical-Biological Sciences, Autonomous University of Guerrero, Guerrero, Mexico.
Cytopathology and Histochemistry Laboratory, Faculty of Chemical-Biological Sciences, Autonomous University of Guerrero, Guerrero, Mexico.
Biomed J. 2021 Dec;44(6 Suppl 2):S171-S178. doi: 10.1016/j.bj.2020.08.012. Epub 2020 Aug 27.
The repressor element 1-silencing transcription factor (REST) is a regulator of gene expression, and the Ras association domain family member 1 A (RASSF1A) is an important tumor suppressor gene involved in cancer development. Although extensive characterization of the roles of REST and RASSF1A in cancer development have been reported in cellular models, the link between them and their possible role in the development of squamous intraepithelial lesions (SIL) and squamous cell carcinoma (SCC) of the cervix have not been explored. The aim of this study was to evaluate the expression of REST and RASSF1A in cervical cytological and histological samples from patients diagnosed with SIL or SCC and in CC-derived cell lines.
We analyzed the expression of REST and RASSF1A by immunocyto/histochemistry in cervical samples from patients (n = 271) and in cancer cell lines. Data analyses were performed using the Kruskal-Wallis test and generalized linear models.
We identified binding sites for REST in RASSF1A and observed a significant reduction in REST and RASSF1A nuclear expression in samples from patients with high-grade SIL (HSIL) and SCC. For REST, we observed an average decrease of 334 and 423 r.u.d. for HSIL (n = 21) and SCC (n = 18) compared with non-LSIL (n = 72), whereas for RASSF1A, this decrease was 126 and 217 r.u.d., respectively (p < 0.001).
Our results provide evidence of the altered expression of REST and RASSF1A in SIL and SCC, with a significant decrease in HSIL, SCC, and SCC-derived cell lines; findings that can contribute to the diagnosis, prognosis, and post-treatment follow-up of patients diagnosed with SIL or SCC.
阻遏元件 1 沉默转录因子（REST）是一种基因表达调节剂，Ras 相关结构域家族成员 1A（RASSF1A）是一种重要的肿瘤抑制基因，参与癌症的发展。尽管在细胞模型中已经广泛研究了 REST 和 RASSF1A 在癌症发展中的作用，但它们之间的联系及其在宫颈鳞状上皮内病变（SIL）和鳞状细胞癌（SCC）发展中的可能作用尚未得到探索。本研究旨在评估 REST 和 RASSF1A 在经 SIL 或 SCC 诊断的患者的宫颈细胞学和组织学样本以及宫颈来源细胞系中的表达。
我们通过免疫细胞化学/组织化学分析了 271 例患者的宫颈样本和癌症细胞系中 REST 和 RASSF1A 的表达。使用 Kruskal-Wallis 检验和广义线性模型进行数据分析。
我们在 RASSF1A 中鉴定出 REST 的结合位点，并观察到高等级 SIL（HSIL）和 SCC 患者样本中 REST 和 RASSF1A 核表达显著减少。对于 REST，我们观察到 HSIL（n=21）和 SCC（n=18）与非 LSIL（n=72）相比，平均减少了 334 和 423 r.u.d.，而对于 RASSF1A，这种减少分别为 126 和 217 r.u.d.（p<0.001）。
我们的研究结果提供了 SIL 和 SCC 中 REST 和 RASSF1A 表达改变的证据，HSIL、SCC 和 SCC 衍生的细胞系中表达显著减少；这些发现可能有助于诊断、预后和 SIL 或 SCC 患者的治疗后随访。
