2. Academic Validation
  3. RPL22L1 fosters malignant features of cervical cancer via the modulation of DUSP6-ERK axis

RPL22L1 fosters malignant features of cervical cancer via the modulation of DUSP6-ERK axis

  • J Transl Med. 2025 Feb 28;23(1):244. doi: 10.1186/s12967-025-06249-0.
Dongmei Zhang 1 2 3,  Meiqi Zhao 1 2,  Ping Jiang 1 2,  Yunzhen Zhou 1 2,  Xu Yan 1 2,  Chong Zhou 1 2,  Yu Mu 1 2,  Shan Xiao 1 2,  Guohua Ji 1 2,  Nan Wu 1 2,  Donglin Sun 1 2,  Xiaobo Cui 1 2,  Shangwei Ning 4,  Hongxue Meng 5,  Sheng Xiao 6,  Yan Jin 7 8 9
Affiliations

Affiliations

  • 1 Laboratory of Medical Genetics, Harbin Medical University, Harbin, 150081, China.
  • 2 Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China, Harbin Medical University, Harbin, 150081, China.
  • 3 Key Laboratory for Molecular Targeted Drug of Heilongjiang Province, College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
  • 4 College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
  • 5 Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
  • 6 Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • 7 Laboratory of Medical Genetics, Harbin Medical University, Harbin, 150081, China. jinyan@hrbmu.edu.cn.
  • 8 Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China, Harbin Medical University, Harbin, 150081, China. jinyan@hrbmu.edu.cn.
  • 9 State Key Laboratory of Zone Cardiovascular Diseases in China, Harbin Medical University, Harbin, 150081, China. jinyan@hrbmu.edu.cn.
PMID: 40022129 DOI: 10.1186/s12967-025-06249-0
Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords

Cervical cancer; ERK; RPL22L1; Sorafenib.

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