Department of Gynecology, Cangzhou People’s Hospital, Cangzhou, China
Balkan Med J. 2023 Oct 20;40(6):409-414. doi: 10.4274/balkanmedj.galenos.2023.2023-4-66. Epub 2023 Jul 31.
Cervical cancer (CC) is a prevalent gynecological carcinoma, and patients infected with human papillomavirus (HPV) have a higher morbidity rate.
To explore the effects of ETS-like transcription factor 4 (ELK4) in patients with HPV CC.
In vitro cell lines and human-sample study.
The ELK4 levels in human tissue (65 HPV CC tissue and 25 HPV normal cervical tissue) and cell lines (human cervical epithelial immortalized cell line H8 and CC cell lines HeLa [HPV18], CaSki [HPV16], and SiHa [HPV]) were quantified using qRT-PCR and western blot assay. ELK4 knockdown transfection was effective and confirmed by western blotting. The MTT and EDU assays were used to evaluate cell viability and proliferation, respectively. Flow cytometry was used to detect the CC cell cycle stage. Stem cell markers, such as cluster of differentiation 133 (CD133), CD44, and aldehyde dehydrogenase 1, and the cervicospheres formed were measured. ChIP-qPCR and luciferase activity experiments were used to assess the bond between ELK4 and F-box protein 22 (FBXO22).
ELK4 was highly expressed in the HPV CC tissue. CC cells with ELK4 knockdown had lower viability and proliferation than the control cells. ELK4 knockdown blocked the progression of the cell cycle from G1 to S phase. ELK4 knockdown suppressed the stem cell-like characteristics of the HPV CC cells. ELK4 bonded with the FBXO22 promoter, inhibiting the levels of phosphatase and tensin homolog (PTEN).
ELK4 facilitated cell cycle progression and stem cell-like characteristics by regulating the FBXO22/PTEN axis. Thus, ELK4 could be a potential therapeutic target to arrest the progress of HPV-associated CC.
宫颈癌（CC）是一种常见的妇科癌，人乳头瘤病毒（HPV）感染患者的发病率更高。
探讨 ETS 样转录因子 4（ELK4）在 HPV CC 患者中的作用。
体外细胞系和人体样本研究。
使用 qRT-PCR 和 Western blot 检测人组织（65 例 HPV CC 组织和 25 例 HPV 正常宫颈组织）和细胞系（人宫颈上皮永生化细胞系 H8 和 CC 细胞系 HeLa[HPV18]、CaSki[HPV16]和 SiHa[HPV]）中的 ELK4 水平。ELK4 敲低转染通过 Western blot 验证有效。MTT 和 EDU 测定分别用于评估细胞活力和增殖。流式细胞术用于检测 CC 细胞周期阶段。测量干细胞标志物，如 CD133、CD44 和醛脱氢酶 1，以及形成的宫颈球体。ChIP-qPCR 和荧光素酶活性实验用于评估 ELK4 与 F-box 蛋白 22（FBXO22）之间的结合。
ELK4 在 HPV CC 组织中高表达。ELK4 敲低的 CC 细胞比对照细胞具有更低的活力和增殖能力。ELK4 敲低阻止了细胞周期从 G1 期向 S 期的进展。ELK4 敲低抑制了 HPV CC 细胞的干细胞样特征。ELK4 与 FBXO22 启动子结合，抑制磷酸酶和张力蛋白同源物（PTEN）的水平。
ELK4 通过调节 FBXO22/PTEN 轴促进细胞周期进程和干细胞样特征。因此，ELK4 可能是阻止 HPV 相关 CC 进展的潜在治疗靶点。
