Inhibition of KIF22 suppresses cancer cell proliferation by delaying mitotic exit through upregulating CDC25C expression

Abstract

KIF22 is a microtubule-dependent molecular motor protein with DNA-binding capacity. It is well known that KIF22 plays a critical role in cell mitosis as a motor protein; however, the role of altered KIF22 expression and its transcriptional regulatory function in cancer development have not yet been defined. This study showed that KIF22 was overexpressed in human cancer tissues, and inhibition of KIF22 significantly led to accumulation of cells in the G2/M phases, resulting in suppression of cancer cell proliferation. The investigation of the molecular mechanisms demonstrated that cell division cycle 25C (CDC25C) is a direct transcriptional target of KIF22, and inhibition of KIF22 increased CDC25C expression and cyclin-dependent kinase 1 (CDK1) activity, resulting in delayed mitotic exit. Phosphorylation of KIF22 was required for its transcriptional regulatory function and the reduction of CDK1 activity. Thus, we conclude that inhibition of KIF22 suppresses cancer cell proliferation by delaying mitotic exit through the transcriptional upregulation of CDC25C.

Increased KIF15 Expression Predicts a Poor Prognosis in Patients with Lung Adenocarcinoma

“…KIF18A is upregulated in breast cancer, colorectal cancer, hepatocellular carcinoma, and renal cell carcinoma; its overexpression correlates with cancer development, carcinogenesis, and poor prognosis [17,[24][25][26][27]. KIF22 is upregulated in human breast tumor tissues, and its inhibition leads to a significant accumulation of cells in the G2/M phase, resulting in suppressed cancer cell proliferation [28]. Previous studies of KIF15 provided a rationale to evaluate the potential relationship between its expression and the prognosis of patients with lung cancer; KIF15 is overexpressed in breast cancer, pancreatic cancer, and LUAD, and therefore represents a potential therapeutic target.…”

Pediatric dilated cardiomyopathy hearts display a unique gene expression profile

“…Moreover, RT-PCR analysis showed a significant age-dependent dysregulation in expression of several genes (Supplemental Table 4), indicating that age of disease onset may affect DCM phenotype in pediatric patients. Expression of dysregulated genes was filtered to detect genes specifically involved in signal transduction; enrichment of genes involved in cell cycle progression and pluripotency stem cell signalling was observed (Table 2) and include CCND1 (P = 0.0023) (22), CCND2 (P = 0.00025) (22), CUX1 (P = 0.00468) (23), kinesin-like protein 22 (KIF22) (P = 0.006) (24), chromobox protein homologue 7 (CBX7) (P = 0.0057) (25), KLF2 (P = 0.003) (26), HMGB2 (P = 0.043) (27), and DDX17 (P = 0.05) (28). Additionally, TBX5 (P = 0.015) and GATA6 (P = 0.0038) were upregulated, both of which have been implicated in reprogramming of pluripotent stem cells (13,29).…”

Podocyte p53 Limits the Severity of Experimental Alport Syndrome

“…Interestingly, up-regulation of genes such as Cdc2a, Cdkn3, Pbk, Rspo1, Kif20a, Kif22, Kif11, Racgap1, and Ube2t correspond to several types of tumors. [21][22][23][24][25][26][27][28] These results suggested that the alteration toward a more proliferative gene-expression pattern underlies the development of glomerular hyperplastic phenotype in AS mice, and that pod-p53 may directly or indirectly influence this change.(mean6SEM, n=3). (L) Primary GECs from p53 +/+ or 2/2 mouse were treated with 25 mM nutlin-3a for 24 hours and protein lysate was extracted.…”