2. Academic Validation
  3. RLIG1 promotes triple-negative breast cancer proliferation by activating mTORC1 signal pathway by interacting with ERK

RLIG1 promotes triple-negative breast cancer proliferation by activating mTORC1 signal pathway by interacting with ERK

  • Cell Signal. 2025 Oct:134:111969. doi: 10.1016/j.cellsig.2025.111969.
Qingqing Wang 1,  Fengxia Chen 2,  Bo Pei 3,  Guojun Jiang 4,  Qianqian Yang 5,  Lu Xu 6,  Yu Gao 1,  Jing Su 1,  Guojin Huang 7,  Fuxiang Zhou 8,  Zeming Li 9
Affiliations

Affiliations

  • 1 Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China; Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, China; Hubei Clinical Cancer Study Center, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, China.
  • 2 Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.
  • 3 Department of Oncology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, Hubei 445000, China; Department of Radiation Oncology and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.
  • 4 Department of Pharmacy, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541199, China.
  • 5 Department of Pathology, Wuhan University Zhongnan Hospital, Wuhan, Hubei 430071, China.
  • 6 Department of Oncology, Yichang Central People's Hospital and The First College of Clinical Medical Science, China Three Gorges University Yichang, Tumor Prevention and Treatment Center and Cancer Research Institute of Three Gorges University, Yichang, Hubei 443008, China.
  • 7 Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Guilin Medical University, Guilin, Guangxi 541001, China. Electronic address: hgjj@163.com.
  • 8 Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China; Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, China; Hubei Clinical Cancer Study Center, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, China. Electronic address: happyzhoufx@sina.com.
  • 9 Medical Department, Wuhan Fourth Hospital, Wuhan, Hubei 430030, China. Electronic address: dr_zemingli@163.com.
PMID: 40582436 DOI: 10.1016/j.cellsig.2025.111969
Abstract

Background: The prognosis of triple-negative breast Cancer (TNBC) is notably unfavorable, necessitating the development of novel treatments to enhance therapeutic outcomes. The underlying mechanisms contributing to the pathogenesis of TNBC remain incompletely understood. RNA 5'-phosphate and 3'-OH Ligase 1 (RLIG1) was found to be the first RNA Ligase in humans and may be related to Cancer development, but no reports have been reported. We observe RLIG1 elevated expression levels in TNBC tissues compared to adjacent non-cancerous tissues, with high RLIG1 expression correlating with reduced overall survival in TNBC patients.

Methods: We investigated RLIG1 in TNBC using bioinformatics tools, cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), colony formation, flow cytometry, and western blotting. Mechanistic insights were gained via mass spectrometry, co-immunoprecipitation, and immunofluorescence.

Results: Here, we found that interfering with RLIG1 can effectively hinder tumor cell cycle progression and proliferation in vitro, as well as inhibit tumor growth in vivo. Mechanistically, RLIG1 was identified as an oncogene that stimulates the mTORC1 signaling pathway in TNBC cells. Furthermore, the interaction between RLIG1 and ERK was confirmed, with RLIG1 promoting cell cycle transition and proliferation through mediating ERK phosphorylation.

Conclusions: Our research offers novel insights into the biological role of RLIG1, indicating its potential as a therapeutic target for TNBC.

Keywords

ERK; Proliferation; RLIG1; TNBC; mTORC1.

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