LEM domain containing 1 (LEMD1) transcriptionally activated by SRY-related high-mobility-group box 4 (SOX4) accelerates the progression of colon cancer by upregulating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway.

Ding Li, Ding Wang, Haofeng Liu, Xiaohui Jiang

Bioengineered 2022 Apr

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Colon cancer is a highly malignant tumor in the digestive system. LEM domain containing 1 (LEMD1) is supposed to be a survival marker of poor prognosis in colon cancer. We aimed to explore the role and mechanism of LEMD1 in colon cancer progression. GEPIA database analyzed LEMD1 expression in colon cancer tissues and prognosis of colon cancer patients. LEMD1 expression in tumor cells was tested by RT-qPCR and western blotting. Proliferation of colon cancer cells was estimated by CCK-8 and colony formation assays. Transwell and wound healing assays were used to appraise the cell invasion and migration. Meanwhile, tube formation assays were used to evaluate angiogenesis. The possible binding sites between SRY-related high-mobility-group box 4 (SOX4) and LEMD1 were predicted by JASPAR database. Besides, SOX4 expression in colon cancer tissues and the correlation between SOX4 and LEMD1 were examined using the GEPIA database. Luciferase reporter and ChIP assays were used to verify the interaction between SOX4 and LEMD1. The expression of proteins in PI3K/Akt signaling was evaluated by western blotting. LEMD1 was overexpressed in colon cancer tissues and cells and associated with poor prognosis. Functionally, LEMD1 deficiency impeded the proliferation, migration, invasion and angiogenesis of colon cancer cells. Additionally, SOX4 had a positive correlation with LEMD1 and could bind to LEMD1 promoter. Rescue assays validated that SOX4 elevation reversed the suppressive role of LEMD1 deletion in the development of colon cancer and the expression of p-PI3K and p-AKT. Collectively, LEMD1 induced by SOX4 drove the progression of colon cancer by activating PI3K/Akt signaling.

Citation

Ding Li, Ding Wang, Haofeng Liu, Xiaohui Jiang. LEM domain containing 1 (LEMD1) transcriptionally activated by SRY-related high-mobility-group box 4 (SOX4) accelerates the progression of colon cancer by upregulating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Bioengineered. 2022 Apr;13(4):8087-8100