SOX7 inhibits colorectal cancer proliferation, invasion and migration through the SHP-2/Wnt/β-catenin/ROS pathway

Acta Universitatis Medicinalis Anhui 2024 07 v.59 1237-1243     font:big middle small

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Authors:Wu Xueliang; Wang Likun; Ma Hongqing; Li Shaodong; Liang Yan; Hui Zhilong; Han Lei; Xue Jun

Keywords:colorectal cancer;SOX7;ROS;SHP-2;Wnt/β-catenin;proliferation;invasion;migration

DOI:10.19405/j.cnki.issn1000-1492.2024.07.020

〔Abstract〕 Objective To investigate the molecular mechanisms by which SOX7 regulates the SHP-2/Wnt/β-catenin/ROS pathway, affecting the proliferation, invasion, and migration of colorectal cancer cells. Methods Twenty nude mice with subcutaneously transplanted tumor models were randomly divided into four groups: SOX7 NC(n=5),SOX mimic(n=5),SOX7 NC+PHPS1(n=5),and SOX7 mimic+PHPS1(n=5) to observe tumor growth.Human colorectal cancer cell line SW480 cells were transfected via lipofection and divided into six groups: SOX7 NC,SOX7 mimic, SOX7 NC+H2O2,SOX7 mimic+H2O2,SOX7 NC+PHPS1,and SOX7 mimic+PHPS1.The expression of SHP-2/Wnt/β-catenin/ROS pathway-related proteins in SW480 cells of each group was detected by Western blot.The invasion and migration capabilities of SW480 cells were assessed through scratch and Transwell invasion assays, while cell proliferation was evaluated using CCK-8. Results In vivoexperiments demonstrated that tumors in the SOX7 mimic group were significantly smaller than those in the SOX7 NC group(P<0.01).Tumors treated with PHPS1 intervention exhibited a significant increase in volume.There was no statistical significance in the difference in tumor volume between the SOX7 mimic+PHPS1 group and the SOX7 NC+PHPS1 group.In vitroexperiments revealed that SOX7 mimic inhibited the expression of Wnt, β-catenin, NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins(P<0.01),and promoted the expression of p-SHP-2 protein(P<0.01).The addition of hydrogen peroxide and SHP-2 inhibitor reversed the effects of SOX7 on SW480 cells(P<0.05),and significantly promoted the expression levels of Wnt, β-catenin, NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins, with no significant difference, while significantly reducing the expression levels of SHP-2,p-SHP-2 proteins, with no significant difference.PHPS1 inhibited the expression of SHP-2,p-SHP-2 proteins(P<0.05) and upregulated the expression of Wnt, β-catenin, NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins(P<0.05).Scratch, Transwell invasion and migration assays, and CCK-8 experiments indicated that SOX7 suppressed the migration, invasion, and proliferation of SW480 cells through oxidative stress and the SHP-2 pathway(P<0.01),while H2O2and PHPS1 intervention promoted the migration, invasion, and proliferation of SW480 cells(P<0.05). Conclusion SOX7 can suppress the proliferation, invasion, and migration of colorectal cancer by targeting the SHP-2/Wnt/β-catenin/ROS pathway.