KIFC1 overexpression promotes pancreatic carcinoma progression via the BUB1/WNT/β- catenin pathway

Background: Pancreatic cancer (PC) is a highly lethal tumor of the gastrointestinal tract. New molecular targets are urgently needed for its treatment. Kinesin family member C1 (KIFC1) is implicated in the development and progression of several types of cancer. Previously, our studies indicated that KIFC1 is overexpressed in hepatocellular carcinoma and activates the malignant behavior of hepatocellular carcinoma through the PI3K/AKT pathway. However, the molecular and functional mechanisms of KIFC1 in PC have not been investigated. Methods: In this study, high-throughput sequencing technology was utilized to characterize differential gene expression profiles in patients with PC. KIFC1 was revealed by screening up-regulated genes from our sequenced data and the Gene Expression Omnibus (GEO) database. Sixty-two PC tissues were analyzed to determine the correlation of KIFC1 expression with the clinicopathological features and prognosis of patients. The role of KIFC1 in proliferation, migration and invasion in PC was verified both in vitro and in vivo. Bioinformatics analysis, coimmunoprecipitation (CoIP), and western blotting were performed to identify proteins that interact with KIFC1and further affect the downstream pathway. Results: According to high-throughput sequencing and the GEO database, KIFC1 is highly expressed in PC. KIFC1 is highly expressed in PC tissues and cells and is positively correlated with poor patient prognosis and malignant cellular behavior. Silencing KIFC1 inhibited the proliferation, migration, and invasion of PC cells, and overexpression of KIFC1 had the opposite effect. Protein‒protein interaction (PPI) and Co-IP analyses indicated that KIFC1 interacts with and regulates BUB1. Overexpression of BUB1 can also promote the proliferation, migration, and invasion of PC cells. BUB1 acts as an intermediary in the activation of the Wnt/β-catenin pathway by KIFC1, leading to an increase in the malignant behaviors of PC cells. The reversal of Wnt/β-catenin activation and increase in cellular malignant behavior induced by KIFC1 overexpression are achieved by silencing BUB1. These biological functions of KIFC1 in PC were also confirmed in a nude mouse xenograft model. Conclusions: Our experiments demonstrated for the first time that KIFC1 can influence PC progression by regulating BUB1 to activate the Wnt/β-catenin pathway. Therefore, KIFC1 shows promise as an attractive therapeutic target for PC in the future.