2. Academic Validation
  3. C1QBP forms a positive feedback loop with the PAICS/FAK/C-MYC axis to promote cancer cell proliferation

C1QBP forms a positive feedback loop with the PAICS/FAK/C-MYC axis to promote cancer cell proliferation

  • Oncogene. 2025 Sep 30. doi: 10.1038/s41388-025-03568-w.
Xiang Cheng # 1 2,  Mengmeng Wang # 1 3 4,  Wei Li 5,  Bingzhang Tian 6,  Jing Zhang 7,  Chen Zhang 8,  Pian Liu 9 10 11
Affiliations

Affiliations

  • 1 Cancer center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 2 Department of Digestive Surgical Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 3 Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 4 Hubei Key Laboratory of Precision Radiation Oncology, Hubei, 430022, China.
  • 5 Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
  • 6 Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, Changsha, Hunan Province, China.
  • 7 Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. zjiris@163.com.
  • 8 Liver Transplant Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. zhang_chen@hust.edu.cn.
  • 9 Cancer center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. liupian@hust.edu.cn.
  • 10 Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. liupian@hust.edu.cn.
  • 11 Hubei Key Laboratory of Precision Radiation Oncology, Hubei, 430022, China. liupian@hust.edu.cn.
  • # Contributed equally.
PMID: 41028903 DOI: 10.1038/s41388-025-03568-w
Abstract

The cell membrane, as the boundary of the cellular system, plays an extremely important role in the regulation of cellular metabolism, substance transport, information exchange and cellular immunity. Complement component 1q subcomponent binding protein (C1QBP) is a ubiquitously expressed cellular protein, and although multiple studies have suggested that C1QBP may play an important role in Cancer, the functions and mechanisms of C1QBP in the progression of many tumors remain unknown. We performed bioinformatics analysis and found that C1QBP was significantly overexpressed in a variety of tumor tissues and that high C1QBP expression correlates strongly with poor prognosis in tumor patients. Further validation in cholangiocarcinoma(CCA) revealed that C1QBP is the most upregulated membrane protein in CCA, where it is involved in energy metabolism, DNA repair, and tolerance to platinum-based chemotherapeutic agents. It also correlates strongly with CCA proliferation and poor prognosis, while silencing of C1QBP significantly inhibits CCA growth in mice. Mechanistic studies further demonstrated that c-Myc can upregulate C1QBP expression at the transcriptional level, subsequently influencing PAICS/FAK expression and promoting CCA growth. Interestingly, C1QBP also regulates c-Myc expression by increasing FAK phosphorylation, establishing a positive feedback loop that drives tumor progression. Additionally, we developed a novel siRNA delivery system, HA gel-siC1QBP, by encapsulating siC1QBP within hyaluronic acid-dopamine hydrogel-coated liposomes. In vivo experiments confirmed its ability to provide prolonged and stable C1QBP inhibition along with enhanced antitumor efficacy. In conclusion, our study suggests that C1QBP may serve as a valuable biomarker for tumour prognosis and that silencing C1QBP using HA gel-siC1QBP -either alone or combined with targeted/ immunotherapies -represents a promising therapeutic strategy against tumors.

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