Steroid 5α-Reductase Type I Induces Cell Viability and Migration via Nuclear Factor-κB/Vascular Endothelial Growth Factor Signaling Pathway in Colorectal Cancer

Frontiers in Oncology

Mengjie Guo¹  Sixia Zhong¹  Ye Yang¹  Chunyan Gu¹  Suyu Wang¹  Li Qiao²  Rongfang Wei²  Miaomiao Shao²  Bin Jiang² 

[1] Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China;;School of Medicine &The Third Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China;

关键词: colorectal cancer;    steroid 5-alpha-reductase type I;    cell viability;    migration;    nuclear factor-κB/vascular endothelial growth factor;    diagnosis;   

DOI  :  10.3389/fonc.2020.01501

来源: DOAJ

【 摘 要 】

Colorectal cancer (CRC) is a common malignant tumor of the digestive system. Steroid 5α-reductase type I (SRD5A1), as an important part of the steroid metabolism, converts testosterone to dihydrotestosterone and regulates sex hormone levels, which accommodates tumor occurrence or development. However, the underlying molecular mechanism of SRD5A1 in CRC remains unclear. We compared SRD5A1 expression in CRC tissues with normal controls by immunohistochemistry and found that elevated SRD5A1 in CRC was relevant for poor patient prognosis. Furthermore, inducible downregulation of SRD5A1 by small hairpin RNA reduced cell viability, promoted cell cycle arrest, and induced cell apoptosis and cellular senescence of CRC cells, as well as attenuated cell migration ability. In the following experiments, we used dutasteride (an inhibitor of SRD5A1/2) to explore its inhibitory effect on the biological processes of CRC cells, as mentioned earlier. Further mechanism study demonstrated that the repression of SRD5A1 abolished the expression of p65 and vascular endothelial growth factor, suggesting that SRD5A1 might regulate cell viability and migration through nuclear factor-κB/vascular endothelial growth factor signaling pathway. Collectively, these findings implicate SRD5A1 acting as a novel biomarker for CRC diagnosis and prognosis and provide compelling evidence for the future evaluation of dutasteride as a promising candidate for CRC treatment.

【 授权许可】

Unknown