Abstract
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.
Highlights
Colorectal cancer (CRC) is the second most commonly diagnosed cancer, and there are 145,600 new cases and 51,020 deaths in the United States in 2019 [1]
Knockdown experiments for CDC28 protein kinase regulatory subunit 1B (CKS1B) showed significant cell growth and migration suppression, suggesting that CKS1B may function as an oncogene in CRC
CKS1B interacts with cyclin and cyclin-dependent kinases (CDKs) to regulate the cell cycle
Summary
Colorectal cancer (CRC) is the second most commonly diagnosed cancer, and there are 145,600 new cases and 51,020 deaths in the United States in 2019 [1]. CDC28 protein kinase regulatory subunit 1B (CKS1B) is a member of the conserved cyclin kinase subunit 1 (CKS1) protein family that interacts with cyclin-dependent kinases (CDKs) and plays important roles in cell cycling [5,6]. The expression of miRNAs can be regulated in part by epigenetic factors such as histone modification and DNA methylation, and miRNA dysregulation via disruption of the balance between miRNAs and their target genes has been reported in cancer development [19,20]. We investigated the roles of microRNAs in regulating CKS1B gene expression in CRC. We present experimental evidence showing that miR-1258 plays a tumor-suppressive role by directly regulating the expression of the oncogenic CKS1B gene in CRC
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