HSPA5 Promotes the Proliferation, Metastasis and Regulates Ferroptosis of Bladder Cancer

  • Int J Mol Sci. 2023 Mar 7;24(6):5144. doi: 10.3390/ijms24065144.
Qinghua Wang  1 Shuai Ke  1 Zelin Liu  2 Haoren Shao  1 Mu He  1 Jia Guo  1
Affiliations
  • 1. Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
  • 2. Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, China.
Abstract

Heat shock protein family A (HSP70) member 5 (HSPA5) is aberrantly expressed in various tumors and closely associated with the progression and prognosis of Cancer. Nevertheless, its role in bladder Cancer (BCa) remains elusive. The results of our study demonstrated that HSPA5 was upregulated in BCa and correlated with patient prognosis. Cell lines with low expression level of HSPA5 were constructed to explore the role of this protein in BCa. HSPA5 knockdown promoted Apoptosis and retarded the proliferation, migration and invasion of BCa cells by regulating the VEGFA/VEGFR2 signaling pathway. In addition, overexpression of VEGFA alleviated the negative effect of HSPA5 downregulation. Moreover, we found that HSPA5 could inhibit the process of Ferroptosis through the P53/SLC7A11/GPX4 pathway. Hence, HSPA5 can facilitate the progression of BCa and may be used as a novel biomarker and latent therapeutic target in the clinic.

Keywords
HSPA5; VEGFA/VEGFR2; bladder cancer; ferroptosis; metastasis; proliferation.
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