文献类型：期刊文献

英文题名：DHCR7: from sterol biosynthesis to oncogenic role in colorectal cancer

作者：Zhou, Chuan[1,2];Wang, Jia[3];He, Han[4];Wang, Chao[5];Zhang, Yunfeng[4];Zhang, Wenbo[3];Wei, Bin[6];Da, Mingxu[2,4];Pang, Minghui[1]

第一作者：Zhou, Chuan

通信作者：Pang, MH[1]

机构：[1]Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Geriatr Gen Surg, Chengdu, Sichuan, Peoples R China;[2]Lanzhou Univ, Gansu Prov Hosp, NHC Key Lab Diag & Therapy Gastrointestinal Tumor, Lanzhou, Gansu, Peoples R China;[3]Gansu Univ Chinese Med, Clin Med Coll 1, Lanzhou, Gansu, Peoples R China;[4]Lanzhou Univ, Clin Med Coll 1, Lanzhou, Gansu, Peoples R China;[5]Shaanxi Prov Peoples Hosp, Dept Urol, Xian, Shaanxi, Peoples R China;[6]Fudan Univ, Inst Translat Brain Res, MOE Frontiers Ctr Brain Sci, State Key Lab Med Neurobiol, Shanghai, Peoples R China

第一机构：Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Geriatr Gen Surg, Chengdu, Sichuan, Peoples R China

通信机构：[1]corresponding author), Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Geriatr Gen Surg, Chengdu, Sichuan, Peoples R China.

年份：2025

卷号：13

外文期刊名：PEERJ

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001626926800001)】；

基金：We gratefully acknowledge the invaluable support and assistance provided by the dedicated staff at Gansu Provincial Hospital, Sichuan Provincial People's Hospital, Fudan University, Lanzhou University, and the University of Electronic Science and Technology of China, whose contributions were essential to the successful completion of this study. We greatly appreciate Haoxuan Lv's help and support with this study.

语种：英文

外文关键词：7-Dehydrocholesterol reductase (DHCR7); Colorectal cancer; PI3K/AKT/mTOR signaling; Oncogenesis

摘要：Objective 7-Dehydrocholesterol reductase (DHCR7) is an enzyme that plays a crucial regulatory role in sterol biosynthesis and has been implicated in tumorigenesis and progression. This study aims to elucidate the biological function of DHCR7 in the pathogenesis of colorectal cancer (CRC). Methods By integrating multi-omics data (including public genomic databases and mass spectrometry data from clinical samples) and establishing in vivo and in vitro experimental systems (encompassing animal models and CRC cell lines with gene overexpression and knockdown), we systematically investigated the functional role of DHCR7 in CRC. A multimodal research strategy combining bioinformatics analysis with molecular biology experiments (Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), western blotting, immunohistochemistry, etc.), proteomics analysis (liquid chromatography-mass spectrometry), and cellular functional assays (proliferation, apoptosis, migration, and invasion) was employed. Results Elevated levels of sterols were observed in CRC tumor tissues, and high cholesterol levels were found to promote the malignant phenotype of tumor cells. Mass spectrometry revealed that DHCR7 was significantly upregulated in CRC tissues and correlated with poor clinical prognosis. DHCR7 could modulate the cholesterol levels in CRC cells; overexpression of this gene enhanced cell proliferation, inhibited apoptosis, and promoted invasion and migration. Conversely, inhibition of DHCR7 expression abrogated these pro-tumorigenic effects, which was consistent with the inactivation of the PI3K/AKT/mTOR signaling pathway and confirmed by pathway reactivation experiments. DHCR7 deficiency significantly reduced tumorigenicity in vivo. Conclusion DHCR7 regulates the progression of CRC both in vitro and in vivo through the PI3K/AKT/mTOR signaling axis and affects the cholesterol levels in CRC.