Liver cancer is the fourth leading cause of cancer-related deaths worldwide, specifically in North America and China, posing not only a serious threat to human health but also a heavy burden on healthcare costs [1]. In the context of an overall decreasing trend in cancer mortality, the mortality associated with liver cancer continues to rise [2]. Hepatocellular carcinoma (HCC) comprises approximately 75–85% of all cases [3]. Most patients with HCC are diagnosed at an advanced stage and systemic therapy is the only option to improve survival, but treatment outcomes in clinical practice remain unsatisfactory [4,5]. The overall prognosis of HCC remains poor for several reasons, including resistance to drugs, tumor metastasis, and tumor recurrence. These clinical challenges suggest that HCC patients need to be precisely stratified according to certain molecular markers and treated with appropriate therapeutic regimens.

Kinesin, a >40-member superfamily of genes, has critical roles in tumor development and progression, such as the regulation of intracellular transport and induction of cell division [6,7]. KIFC3, one of the kinesin-14 members, is a minus end-directed kinesin motor that drives the motion of microtubules. It has been previously shown that KIFC3 is important for the onset of mitotic spindle assembly [8,9] and intracellular transport by regulating microtubule-microtubule crosslinking or sliding over the past few years [10,11]. Apart from these features, several studies have shown that KIFC3 also plays important roles in esophageal squamous cell carcinoma (ESCC), colorectal cancer and chemotherapeutic drug resistance [9,[12], [13], [14], [15]]. The data from public databases suggested that the expression of KIFC3 is upregulated in gastrointestinal tumors. However, the expression and function of KIFC3 in HCC have not been investigated.

Meanwhile, overactivation of the PI3K/AKT signalling pathway has been shown to be a crucial pathway promoting the development of HCC and is associated with poor prognosis, especially in patients with metabolic dysregulation [[16], [17], [18]]. Multiple studies have confirmed the critical role of the PI3K/AKT pathway involved in the angiogenesis, Epithelial-mesenchymal transition (EMT) development, and drug resistance in HCC [17]. EMT has also been recognized as a key mediator of tissue regeneration, inflammation, fibrosis, and cancer metastasis [19]. After undergoing the EMT process, cells acquire enhanced motility and can cross the basement membrane and stromal tissue to access the vasculature and circulation [20].

In this study, we investigated for the first time the correlation between KIFC3 expression and the progression of HCC, as well as the possible function of EMT and the PI3K/AKT signal pathway. Additionally, we demonstrated for the first time the interaction of KIFC3 and TRIP13 in the progression of HCC, aiming to find a novel biomarker and a therapeutic target for HCC.