KIF4A Regulates the Progression of Pancreatic Ductal Adenocarcinoma through Proliferation and Invasion
Open Access
- 11 November 2021
- journal article
- research article
- Published by Hindawi Limited in BioMed Research International
- Vol. 2021, 1-12
- https://doi.org/10.1155/2021/8249293
Abstract
Background. Pancreatic cancer is a malignant tumor of the digestive tract, which is difficult to diagnose and treat due to bad early diagnosis. We aimed to explore the role of kinesin superfamily 4A (KIF4A) in pancreatic ductal adenocarcinoma (PDAC). Methods. We first used the bioinformatic website to screen the data of pancreatic cancer in TCGA, and KIF4A protein was detected among the 86 specimens of patients in our hospital combined with clinic-pathological characteristics and survival analysis. KIF4A loss-expression cell lines were established by RNA interference (RNAi). In addition, we performed in vitro cell assays to detect the changes in cell proliferation, migration, and invasion. The proteins involved in the proliferation and metastasis of cancer cells were also detected by western blot. The above results could be proved in vivo. Further, the correlation between KIF4A and CDC5L was analyzed by TCGA and IHC data. Results. We first found a high expression of KIF4A in pancreatic cancer, suggesting a role of KIF4A in the development of pancreatic cancer. KIF4A was found to be differentially expressed ( ) among the 86 specimens of patients in our hospital and was significantly associated with PDAC TNM stages and tumor size. High KIF4A expression also significantly worsened overall survival (OS) and disease-free survival rate (DFS) ( , respectively). In addition, cell proliferation, migration, and invasion were inhibited by the KIF4A-shRNA group compared with the control ( , respectively). In the end, knockdown of KIF4A could inhibit tumor development and metastasis in vivo. Further, the positive correlation between KIF4A and CDC5L existed, and KIF4A might promote pancreatic cancer proliferation by affecting CDC5L expression. Conclusion. In conclusion, the high expression level of KIF4A in PDAC was closely related to poor clinical and pathological status, lymphatic metastasis, and vascular invasion. KIF4A might be involved in promoting the development of PDAC in vitro and in vivo, which might be a new therapeutic target of PDAC.Funding Information
- National Natural Science Foundation of China (81702534, 81701840, 81401957)
This publication has 37 references indexed in Scilit:
- Aurora B suppresses microtubule dynamics and limits central spindle size by locally activating KIF4AThe Journal of cell biology, 2013
- Human chromokinesins promote chromosome congression and spindle microtubule dynamics during mitosisThe Journal of cell biology, 2012
- Clinical aspect and molecular mechanism of DNA aneuploidy in gastric cancersThe Esophagus, 2012
- KIF4 Regulates Midzone Length during CytokinesisCurrent Biology, 2011
- How kinesin motor proteins drive mitotic spindle function: Lessons from molecular assaysSeminars in Cell & Developmental Biology, 2010
- Structural requirements of chromokinesin Kif4A for its proper function in mitosisBiochemical and Biophysical Research Communications, 2008
- The kinesin KIF1Bβ acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressorGenes & Development, 2008
- Activation of KIF4A as a Prognostic Biomarker and Therapeutic Target for Lung CancerClinical Cancer Research, 2007
- Human chromokinesin KIF4A functions in chromosome condensation and segregationThe Journal of cell biology, 2004
- Human kinesin superfamily member 4 is dominantly localized in the nuclear matrix and is associated with chromosomes during mitosisBiochemical Journal, 2001