DHCR7 promotes tumorigenesis via activating PI3K/AKT/mTOR signalling pathway in bladder cancer.

Abstract

Bladder cancer (BCa) is a common malignancy with uncertain molecular mechanism. 7-dehydrocholesterol reductase (DHCR7), the enzyme of mammalian sterol biosynthesis, plays important roles in several types of cancers but its specific function in BCa is still unknown. The current study aimed to determine the bioinformatic characteristics and biological functions of DHCR7 in BCa. Sequencing results and clinical data from online public databases, human BCa tissues and matched noncancerous tissues, xenograft nude mice, DHCR7 deficiency and overexpression BCa cell (T24 and EJ) models were used. Several bioinformatics analyses were made, qRT-PCR, Western-blotting, flow cytometry, immunohistochemistry (IHC), MTT assay, wound healing and cell invasion assays were performed. It was found that DHCR7 was upregulated in BCa as an independent risk factor, and the expression of DHCR7 was associated with BCa grade and stage, finally resulted in poor prognosis. We further demonstrated that DHCR7 overexpression could accelerate the G0/G1 phase to accelerate the growth of tumor cells, antagonize cell apoptosis, and enhance the invasion and migration capacity, as well as EMT process via PI3K/AKT/mTOR signalling pathway, which could be completely reversed by DHCR7 knockdown. Finally, DHCR7 deficiency significantly decreased tumorigenesis in vivo. Our novel data demonstrated that DHCR7 could modulate BCa tumorigenesis in vitro and in vivo via PI3K/AKT/mTOR signalling pathway. It is suggested that DHCR7 might become a molecular target for the diagnosis and treatment of BCa.

• Authors: Yan Li, Yongying Zhou, Mingliu Huang, Zhen Wang, Daoquan Liu, Jianmin Liu, Xun Fu, Shu Yang, Shidong Shan, Liang Yang, Yuhang Guo, Pengfei Ren, Ping Chen, Guang Zeng, Yuming Guo, Xinghuan Wang, Michael E DiSanto, Xinhua Zhang
• Journal: Cellular signalling (Cell Signal) Vol. 102 Pg. 110553 (02 2023) ISSN: 1873-3913 [Electronic] England
• PMID: 36473621 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• Proto-Oncogene Proteins c-akt
• Phosphatidylinositol 3-Kinases
• Oxidoreductases
• TOR Serine-Threonine Kinases
• MTOR protein, human

Topics

• Animals
• Mice
• Humans
• Proto-Oncogene Proteins c-akt (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Oxidoreductases
• Mice, Nude
• Cell Line, Tumor
• Cell Proliferation
• TOR Serine-Threonine Kinases (metabolism)
• Cell Transformation, Neoplastic (metabolism)
• Carcinogenesis
• Urinary Bladder Neoplasms (pathology)
• Cell Movement
• Mammals (metabolism)