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Background: Anchoring filament protein ladinin-1 (LAD1) was related to the aggressive progression of breast, lung, laryngeal and thyroid cancers. However, the association of LAD1 with colorectal cancer remained unknown. Here, to determine the relationship of LAD1 with colorectal cancer progression, we explored the effect of LAD1 loss on the malignant features of colorectal cancer cells.Methods: We constructed LAD1-depleted cell lines and examined the effect of LAD1 deficiency on the phenotypic and molecular features of colorectal cancer cells in vitro. The function of LAD1 in metastasis in vivo was examined by establishing a spleen-to-liver metastasis mouse model. LAD1 protein expression in colorectal cancer patient specimens was assessed by immunohistochemistry of tumor microarrays.Results: We found that LAD1 was abundant in most colorectal cancer cells. In addition, high expression of LAD1 significantly correlated with poor patient outcome. LAD1 depletion inhibited the migration and invasion of two different colorectal cancer cell lines, SW620 and Caco-2, without affecting their proliferation. In addition, LAD1 loss led to defects in liver metastasis of SW620 cells in the mouse model. Immunohistochemistry of colorectal cancer tissues revealed LAD1 enrichment in metastatic tissues compared to that in primary tumor and normal tissues.Conclusion: These results suggest that LAD1 expression is associated with the metastatic progression of colorectal cancer by promoting the migration and invasion of cancer cells. [ABSTRACT FROM AUTHOR]

Increasing evidence has demonstrated that increased expression of cyclin-dependent kinase regulatory subunit 1B (CKS1B) is associated with the pathogenesis of many human cancers, including colorectal cancer (CRC). However, the regulatory mechanisms underlying the expression of CKS1B in CRC are not completely understood. Here, we investigate the role played by microRNAs in the expression of CKS1B and carcinogenesis in CRC. Among the six microRNAs predicted to target CKS1B gene expression, only miR-1258 was revealed to downregulate CKS1B expression through binding to its 3'-UTR region, as ectopic miR-1258 expression suppressed CKS1B expression and vice versa. In CRC, miR-1258 expression also decreased cell proliferation and migration in vitro and tumor growth in vivo, similar to cells with silenced CKS1B expression. Considering the highly increased levels of CKS1B and decreased expression of miR-1258 in tumors from CRC patients, these findings suggest that miR-1258 may play tumor-suppressive roles by targeting CKS1B expression in CRC. However, the therapeutic significance of these findings should be evaluated in clinical settings. [ABSTRACT FROM AUTHOR]