Zhang Dongmei, Zhao Meiqi, Jiang Ping, Zhou Yunzhen, Yan Xu, Zhou Chong, Mu Yu, Xiao Shan, Ji Guohua, Wu Nan, Sun Donglin, Cui Xiaobo, Ning Shangwei, Meng Hongxue, Xiao Sheng, Jin Yan
Laboratory of Medical Genetics, Harbin Medical University, Harbin, 150081, China.
Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China, Harbin Medical University, Harbin, 150081, China.
J Transl Med. 2025 Feb 28;23(1):244. doi: 10.1186/s12967-025-06249-0.
Cervical cancer remains one of the leading causes of cancer-related deaths among women globally, and there is still a need to research molecular targets that can be used for prognosis assessment and personalized molecular therapies. Here, we investigate the role of potential molecular target ribosomal L22-like 1 (RPL22L1) on cervical cancer, identify its potential mechanisms, and explore its related applications in prognosis and molecular therapies.
Multiple cervical cancer cohorts online, tissue microarrays and clinical tissue specimens were analyzed for the association between RPL22L1 expression and patient outcomes. Functional and molecular biology studies of cell and mice models were used to clarify the effects and potential mechanisms of RPL22L1 on cervical cancer.
RPL22L1 is highly expressed in both cervical adenocarcinoma and squamous cell carcinoma, and its expression is significantly associated with histology grade, clinical stage, recurrence, vascular space involvement, tumor sizes and poor prognosis. In vitro and in vivo experiment revealed that RPL22L1 overexpression significantly promoted cervical cancer cell proliferation, migration, invasion, tumorigenicity and Sorafenib resistance, which were attenuated by RPL22L1 knockdown. Mechanistically, RPL22L1 competitively binds to ERK phosphatase DUSP6, leading to excessive activation of ERK. The combined application of ERK inhibitors can effectively inhibit RPL22L1 overexpressing cervical cancer cells both in vivo and in vitro.
RPL22L1 promotes malignant biological behavior of cervical cancer cells by competitively binding with DUSP6, thereby activating the ERK pathway. The combined use of Sorafenib and an ERK inhibitor is a potentially effective molecular targeted therapy for RPL22L1-high cervical cancer.
宫颈癌仍是全球女性癌症相关死亡的主要原因之一，仍需研究可用于预后评估和个性化分子治疗的分子靶点。在此，我们研究潜在分子靶点核糖体L22样蛋白1（RPL22L1）在宫颈癌中的作用，确定其潜在机制，并探索其在预后和分子治疗中的相关应用。
分析多个在线宫颈癌队列、组织芯片和临床组织标本中RPL22L1表达与患者预后之间的关联。利用细胞和小鼠模型的功能及分子生物学研究来阐明RPL22L1对宫颈癌的影响及潜在机制。
RPL22L1在宫颈腺癌和鳞状细胞癌中均高表达，其表达与组织学分级、临床分期、复发、脉管侵犯、肿瘤大小及预后不良显著相关。体外和体内实验表明，RPL22L1过表达显著促进宫颈癌细胞增殖、迁移、侵袭、致瘤性及索拉非尼耐药，而RPL22L1敲低则可减弱这些作用。机制上，RPL22L1竞争性结合ERK磷酸酶DUSP6，导致ERK过度激活。ERK抑制剂联合应用可在体内外有效抑制RPL22L1过表达的宫颈癌细胞。
RPL22L1通过与DUSP6竞争性结合促进宫颈癌细胞的恶性生物学行为，从而激活ERK通路。索拉非尼与ERK抑制剂联合使用是RPL22L1高表达宫颈癌潜在有效的分子靶向治疗方法。
