2. Academic Validation
  3. LncRNA OIP5-AS1 inhibits ferroptosis in prostate cancer with long-term cadmium exposure through miR-128-3p/SLC7A11 signaling

LncRNA OIP5-AS1 inhibits ferroptosis in prostate cancer with long-term cadmium exposure through miR-128-3p/SLC7A11 signaling

  • Ecotoxicol Environ Saf. 2021 Sep 1;220:112376. doi: 10.1016/j.ecoenv.2021.112376.
Yangyi Zhang 1,  Shanqi Guo 2,  Shuo Wang 3,  Xiaojian Li 4,  Dingkun Hou 1,  Hongzheng Li 1,  Lili Wang 1,  Yong Xu 1,  Baojie Ma 5,  Haitao Wang 6,  Xingkang Jiang 7
Affiliations

Affiliations

  • 1 Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, PR China.
  • 2 Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, PR China.
  • 3 The School of Medicine, Nankai University, Tianjin 300071, PR China.
  • 4 Department of Urology, Peking University Shougang Hospital, Beijing 100144, PR China.
  • 5 Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, PR China. Electronic address: scalpeltj@163.com.
  • 6 Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, PR China. Electronic address: peterrock2000@126.com.
  • 7 Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, PR China; The School of Medicine, Nankai University, Tianjin 300071, PR China. Electronic address: Jiangx@tmu.edu.cn.
PMID: 34051661 DOI: 10.1016/j.ecoenv.2021.112376
Abstract

Previous studies suggest that cadmium (Cd) is one of the causative factors of prostate Cancer (PCa), but the effect of chronic Cd exposure on PCa progression remains unclear. Besides, whether long noncoding RNAs (lncRNAs) are involved in the regulation of prolonged exposure to Cd in PCa needs to be elucidated. In the present study, we found that the serum concentration of Cd in PCa patients was positively correlated with the Gleason score and tumor-node-metastasis (TNM) classification. To simulate chronic Cd exposure in PCa, we subjected PC3 and DU145 cells to long-term, low-dose Cd exposure and further examined tumor behavior. Functional studies identified that chronic Cd exposure promoted cell growth and Ferroptosis resistance in vitro and in vivo. Furthermore, we found that lncRNA OIP5-AS1 expression was greatly elevated in PC3 and DU145 cells upon chronic Cd exposure. Dysregulation of OIP5-AS1 expression mediated cell growth and Cd-induced Ferroptosis. Mechanistically, we demonstrated that OIP5-AS1 served as an endogenous Sponge of miR-128-3p to regulate the expression of SLC7A11, a surrogate marker of Ferroptosis. Moreover, miR-128-3p decreased cell viability by enhancing Ferroptosis. Taken together, our data indicate that lncRNA OIP5-AS1 promotes PCa progression and Ferroptosis resistance through miR-128-3p/SLC7A11 signaling.

Keywords

Cadmium; MiR-128-3p; OIP5-AS1; Prostate cancer; SLC7A11.

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