2. Academic Validation
  3. Silencing CALB1 enhances prostate cancer radiosensitivity via calcium-mediated mitochondrial dysfunction and cellular senescence

Silencing CALB1 enhances prostate cancer radiosensitivity via calcium-mediated mitochondrial dysfunction and cellular senescence

  • Cell Calcium. 2025 Aug 26:132:103071. doi: 10.1016/j.ceca.2025.103071.
Chen Gong 1,  Senmao Li 1,  Ye An 2,  Chadanfeng Yang 1,  Zhiyong Tan 1,  Wujie Chen 1,  Dihao Lv 1,  Haichao Wu 3,  Haifeng Wang 1,  Shi Fu 1,  Haihao Li 1,  Yanjie Kong 4,  Yinglong Huang 5,  Mingxia Ding 6
Affiliations

Affiliations

  • 1 Department of Urology, The Second Affiliated Hospital of Kunming Medical University, No. 347 Dianmian Street, Wuhua District, Kunming, 650101, Yunnan, China; Urological disease clinical medical center of Yunnan province, The Second Affiliated Hospital of Kunming Medical University, No. 347 Dianmian Street, Wuhua District, Kunming, 650101, Yunnan, China; Scientific and Technological Innovation Team of Basic and Clinical Research of Bladder Cancer in Yunnan Universities, The Second Affiliated Hospital of Kunming Medical University, No. 347 Dianmian Street, Wuhua District, Kunming, 650101, Yunnan, China.
  • 2 Department of Urology, The First People's Hospital of Yunnan Province, Kunming, 650032, Yunnan, China; The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650500, Yunnan, China.
  • 3 Department of Vascular Surgery, Taizhou Municipal Hospital, No.581 Shifu Avenue(East), Jiaojiang District, Taizhou, 318000, Zhejiang, China.
  • 4 Pathology department, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518035, China. Electronic address: kongyanjie26@163.com.
  • 5 Department of Urology, The Second Affiliated Hospital of Kunming Medical University, No. 347 Dianmian Street, Wuhua District, Kunming, 650101, Yunnan, China; Urological disease clinical medical center of Yunnan province, The Second Affiliated Hospital of Kunming Medical University, No. 347 Dianmian Street, Wuhua District, Kunming, 650101, Yunnan, China; Scientific and Technological Innovation Team of Basic and Clinical Research of Bladder Cancer in Yunnan Universities, The Second Affiliated Hospital of Kunming Medical University, No. 347 Dianmian Street, Wuhua District, Kunming, 650101, Yunnan, China. Electronic address: huangyinglong@kmmu.edu.cn.
  • 6 Department of Urology, The First People's Hospital of Yunnan Province, Kunming, 650032, Yunnan, China; The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650500, Yunnan, China. Electronic address: dingmingxia@kmmu.edu.cn.
PMID: 40902499 DOI: 10.1016/j.ceca.2025.103071
Abstract

Background: Prostate Cancer remains a leading cause of cancer-related deaths in men, with radioresistance limiting treatment efficacy. This study investigates the role of Calbindin 1 (CALB1), a calcium-binding protein regulated by miR-186-5p, in prostate Cancer progression and radiation response.

Methods: CALB1 expression was analyzed using GEO and TCGA datasets, and the regulatory relationship with miR-186-5p was validated. Functional studies including CALB1 knockdown, calcium chelation, and mitochondrial rescue interventions were conducted in prostate Cancer cells, spheroids, and xenograft models, assessing proliferation, senescence, calcium homeostasis, and radiation response.

Results: We identified CALB1 as a target of downregulated miR-186-5p in prostate Cancer. CALB1 silencing inhibited prostate Cancer growth by inducing cellular senescence through calcium dysregulation, mitochondrial dysfunction, and oxidative stress. CALB1 depletion significantly enhanced radiosensitivity both in vitro and in vivo, with calcium chelation or mitochondrial interventions partially rescuing these effects.

Conclusions: CALB1 regulates prostate Cancer progression and radiation response by maintaining calcium homeostasis. Its depletion triggers calcium overload and mitochondrial dysfunction, enhancing radiation sensitivity and identifying CALB1 as a potential therapeutic target.

Keywords

CALB1; Calcium homeostasis; Cellular senescence; Prostate cancer; Radiosensitivity; miR-186-5p.

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