KIF4A facilitates cell proliferation via induction of p21-mediated cell cycle progression and promotes metastasis in colorectal cancer

Abstract

Kinesin family member 4A (KIF4A) was found to be implicated in the regulation of chromosome condensation and segregation during mitotic cell division, which is essential for eukaryotic cell proliferation. However, little is known about the role of KIF4A in colorectal carcinoma (CRC). This study explored the biological function of KIF4A in CRC progression and investigated the potential molecular mechanisms involved. Here, we found that KIF4A was remarkably upregulated in primary CRC tissues and cell lines compared with paired non-cancerous tissues and normal colorectal epithelium. Elevated expression of KIF4A in CRC tissues was significantly correlated with clinicopathological characteristics in patients as well as with shorter overall and disease-free cumulative survival. Multivariate Cox regression analysis revealed that KIF4A was an independent prognostic factor for poor survival in human CRC patients. Functional assays, including a CCK-8 cell proliferation assay, colony formation analysis, cancer xenografts in nude mice, cell cycle and apoptosis analysis, indicated that KIF4A obviously enhanced cell proliferation by promoting cell cycle progression in vitro and in vivo. Furthermore, gene set enrichment analysis, Luciferase reporter assays, and ChIP assays revealed that KIF4A facilitates cell proliferation via regulating the p21 promoter, whereas KIF4A had no effect on cell apoptosis. In addition, Transwell analysis indicated that KIF4A promotes migration and invasion in CRC. Taken together, these findings not only demonstrate that KIF4A contributes to CRC proliferation via modulation of p21-mediated cell cycle progression but also suggest the potential value of KIF4A as a clinical prognostic marker and target for molecular treatments.

<p>KIF4A Promotes Clear Cell Renal Cell Carcinoma (ccRCC) Proliferation in vitro and in vivo</p>

“…28 Additionally, KIF4A promotes the proliferation of colorectal cancer by the regulation of p21-mediated cell cycle progression, and they found KIF4A knockdown obviously decreased the expression level of pAKT, and the expression level of MEK and ERK was comparable, suggesting that KIF4A promotes CRC proliferation through PI3K/AKT signaling pathway. 15 Interestingly, we found that KIF4A contributed to cell proliferation of ccRCC in vitro and in mice. Whether KIF4A promotes ccRCC through this signaling pathway also requires further study.…”

“…14 In recent years, the key role of KIF4A in cancer development has gradually been revealed. 15 KIF4A is widely expressed in a variety of human tissues. 15 Various studies have reported that KIF4A promoted the progression of several cancers, such as cervical cancer and oral cancer.…”

“…15 KIF4A is widely expressed in a variety of human tissues. 15 Various studies have reported that KIF4A promoted the progression of several cancers, such as cervical cancer and oral cancer. 16 In addition, KIF4A promotes cell proliferation via cell cycle regulation and metastasis in colorectal cancer.…”

“…16 In addition, KIF4A promotes cell proliferation via cell cycle regulation and metastasis in colorectal cancer. 15 KIF4A ablation also leads to inhibition of lung cancer cell proliferation. 17 However, it is unclear whether KIF4A is involved in the occurrence and development of ccRCC in highly malignant tumors.…”

Prognostic value of Kinesin‐4 family genes mRNA expression in early‐stage pancreatic ductal adenocarcinoma patients after pancreaticoduodenectomy

“…More importantly, Kinesin-4 family genes could affect tumor biological behavior, such as proliferation, invasion, metastasis, and so on. [22][23][24][25] It is well known that the poor prognosis of tumor depends largely on its malignant behavior. So, we speculated that Kinesin-4 family genes might be associated with pancreatic cancer prognosis.…”