Molecular mechanism of ADAM17-HMGCS1 axis promoting colorectal cancer
WANG Yinge
ZHANG Zhekai
LI Jie
ZHAO Huidong
LI Danxiu
JIN Haifeng
YANG Tao
Abstract：Objective To investigate the molecular mechanism of A disintegrin and metalloproteinase 17(ADAM17)-3-hydroxy-3-methylglutaryl-coa synthase 1(HMGCS1)axis in promoting colorectal cancer(CRC).Methods The expression of ADAM17 in CRC was analyzed by the cancer genome map database,and the impact of ADAM17 on prognosis was analyzed by Kaplan-Meier survival.The shADAM17 stable knockdown cell line was constructed by selecting the CR HUTU80 cell line with high expression of ADAM17,and the ADAM17 overexpression cell line was constructed by using the SW620 cell line with low expression of ADAM17.The in vitro proliferation ability of cells was analyzed through experiments such as CCK-8,plate cloning and cell immunofluorescence detection of proliferating cell nuclear antigen.A subcutaneous transplanted tumor model in nude mice was constructed to evaluate tumorigenicity in vivo.Key differential genes and pathways were screened by transcriptome sequencing,and the molecular regulatory relationships were verified by real-time fluorescence quantitative PCR(RT-qPCR)and Western blot.Results Database analysis indicated that ADAM17 was highly expressed in CRC and was positively correlated with poor prognosis(P<0.05).ADAM17 was highly expressed in HUTU80 cells but lowly expressed in SW620 cells(P<0.05).Knockdown of ADAM17 could significantly inhibit the proliferation of HUTU80 cells,while overexpression of ADAM17 promoted the proliferation of SW620 cells(P<0.05).Subcutaneous transplanted tumor models in nude mice confirmed that knockdown of ADAM17 could inhibit tumor volume and tumor mass(P<0.05).Transcriptome sequencing showed that knockdown of ADAM17 would lead to down-regulation of HMGCS1 expression(P<0.05),and further analysis revealed that lipid metabolism pathways were significantly enriched after ADAM17 knockdown.Western blot and RT-qPCR verified that the protein and mRNA expression of HMGCS1 was positively correlated with ADAM17(P<0.05).Conclusion ADAM17 can drive the proliferation of CRC cells by positively regulating HMGCS1 expression and plays an important role in lipid metabolism pathways.The potential role of the ADAM17-HMGCS1 axis in CRC can provide a new research direction for future targeted therapy,and further verifying the effectiveness of its clinical application will be of great significance.
Keywords：colorectal cancera disintegrin and metalloproteinase 173-hydroxy-3-methylglutaryl-CoA synthase 1lipid metabolismcell proliferationprognosis
Publication Date：2025-10-13
Online Publishing Date：2025-10-21(First online date of this platform, not the publication date of the document)
Pages：9( 47-55 )