Huo Wen, Huang Yiheng, Tian Baoqinq, Chen Xiaozheng, Lu Jie, Huang Xinyi, Wu Meng, Yu Jinming, Chen Dawei, Wang Ruozheng
Department of Radiation Oncology, Affiliated Tumor Hospital of Xinjiang Medical University, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, China.
Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Transl Oncol. 2024 Dec;50:102146. doi: 10.1016/j.tranon.2024.102146. Epub 2024 Oct 7.
RECQL4 is a member of the DNA helicase family and is critical for DNA replication, DNA damage repair, and tumor progression. However, its specific role in cervical cancer remains uncertain.
In this study, we aimed to investigate the impact of RECQL4 on cervical cancer prognosis using clinical specimens from The Cancer Genome Atlas. We evaluated the malignant effects of RECQL4 through various experimental assays including cell Cell Counting Kit-8, EdU, colony formation, cell cycle analysis, cell apoptosis, scratch, and Transwell assays. We explored the mechanisms of RECQL4-regulated malignancy using analyses of bioinformatics, RNA sequencing data, polymerase chain reaction (PCR), western blotting, and cell immunofluorescence experiments. Furthermore, we validated the effects of RECQL4 knockdown on tumor growth using subcutaneous tumor models in nude mice.
RECQL4 was upregulated in cervical cancer and correlated with prognosis, demonstrating a positive relationship with tumor mutational burden. Knockdown of RECQL4 inhibits cervical cancer cell proliferation, migration, and invasion, suppresses epithelial-mesenchymal transition status, induces cell cycle arrest, and promotes apoptosis. Mechanistically, RECQL4 mediated malignancy through the PI3K/AKT pathway and reduced nuclear β-catenin expression. In vivo studies further confirmed that RECQL4 knockout significantly inhibited tumor growth.
Our findings provide novel insights into the mechanism behind RECQL4-mediated cervical cancer progression through the PI3K/AKT pathway. Furthermore, our study suggests potential therapeutic strategies for targeting RECQL4 in cervical cancer treatment.
RECQL4是DNA解旋酶家族的成员，对DNA复制、DNA损伤修复和肿瘤进展至关重要。然而，其在宫颈癌中的具体作用仍不确定。
在本研究中，我们旨在利用来自癌症基因组图谱的临床标本，研究RECQL4对宫颈癌预后的影响。我们通过各种实验分析评估RECQL4的恶性影响，包括细胞计数试剂盒-8、EdU、集落形成、细胞周期分析、细胞凋亡、划痕和Transwell分析。我们使用生物信息学分析、RNA测序数据、聚合酶链反应（PCR）、蛋白质免疫印迹和细胞免疫荧光实验，探索RECQL4调节恶性肿瘤的机制。此外，我们使用裸鼠皮下肿瘤模型验证了敲低RECQL4对肿瘤生长的影响。
RECQL4在宫颈癌中上调并与预后相关，与肿瘤突变负荷呈正相关。敲低RECQL4可抑制宫颈癌细胞的增殖、迁移和侵袭，抑制上皮-间质转化状态，诱导细胞周期停滞，并促进细胞凋亡。机制上，RECQL4通过PI3K/AKT途径介导恶性肿瘤，并降低核β-连环蛋白表达。体内研究进一步证实，敲除RECQL4可显著抑制肿瘤生长。
我们的研究结果为RECQL4通过PI3K/AKT途径介导宫颈癌进展的机制提供了新的见解。此外，我们的研究提出了在宫颈癌治疗中靶向RECQL4的潜在治疗策略。
