Down regulated oncogene KIF2C inhibits growth, invasion, and metastasis of hepatocellular carcinoma through the Ras/MAPK signaling pathway and epithelial-to-mesenchymal transition

Abstract

Background: Hepatocellular carcinoma (HCC) is the leading cause of cancer death. Kinesin family member 2C (KIF2C) has been shown as oncogene in a variety of tumors. However, it's role in HCC remains unclear.Methods: In this study, the expression level of KIF2C in HCC was detected by immunohistochemical staining and RT-PCR, and verified by Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and Oncomine database. A curve was established to evaluate the diagnostic efficiency of KIF2C. The effect of KIF2C on HCC was investigated by flow cytometry, Cell Counting Kit-8, Transwell, and the wound-healing assay. We explored the underlying mechanism through epithelial-to-mesenchymal transition (EMT) and transcriptome sequences analysis.Results: KIF2C was overexpression in HCC tissue and related to neoplasm histologic grade (P<0.001), pathology stage (P=0.001), and a dismal prognosis (overall, recurrence-free, and disease-free survival). The diagnostic efficacy of KIF2C was >90% in diagnosing HCC. The HCC cell function experiments showed that KIF2C promoted HCC cell proliferation, migration, invasion, and an accelerated cell cycle, and inhibited apoptosis. Based on western blot analysis and RT-PCR, we found that KIF2C promoted HCC invasion and metastasis through activation of the EMT. Based on transcriptome sequences, we showed that KIF2C promoted HCC through the Ras/MAPK and PI3K/Akt signaling pathway.Conclusions: KIF2C was found to promote the progression of HCC and is anticipated to serve as a biomarker for HCC diagnosis, prognosis, and targeted therapy.

Large-Scale Transcriptome Data Analysis Identifies KIF2C as a Potential Therapeutic Target Associated With Immune Infiltration in Prostate Cancer

“…Previous research has revealed that KIF2C is substantially expressed in liver cancer (17,19,26,27), breast cancer (28), endometrial carcinoma (20), lung cancer (29,30), glioma (31), bladder cancer (32), colorectal cancer (33), esophageal squamous cell carcinoma (34), cervical cancer (18), and thyroid cancer (35). The results of our pan-cancer analysis indicated that KIF2C was highly expressed in 28 tumors, including PCa, which was consistent with previous results reported in the literature.…”

“…According to Yang et al (18), KIF2C expression was linked to the kind of cervical cancer. In hepatocellular carcinoma, Mo et al found that KIF2C was substantially linked with pathological stage and neoplasm histological grade (17). According to Gan et al, elevated KIF2C expression in NSCLC tissues was associated with a higher T stage, poor differentiation status, and lymph node metastases (29).…”

“…It has been reported that there is a relationship between KIF2C and the MAPK signaling pathway. According to Mo et al (17), the downregulated oncogene KIF2C suppressed the development of hepatocellular carcinoma through the signaling pathway. Furthermore, in a transformed model, knocking down K-Ras or inhibiting ERK1/2 activation lowered KIF2C expression, suggesting that KIF2C might be a potential target for cancer medication treatment (56).…”

“…In a number of malignancies, KIF2C has been recognized as a potential oncogene. According to Mo et al (17), KIF2C enhanced hepatocellular cancer through the Ras/MAPK and PI3K/Akt signaling pathways. According to Yang et al (18), KIF2C may accelerate the growth of cervical cancer by blocking the stimulation of the p53 signaling pathway.…”

KIF2C is a Biomarker Correlated With Prognosis and Immunosuppressive Microenvironment in Human Tumors

“…KIF2C is upregulated in endometrial cancer (EC), which can cause a malignant phenotype in EC and negatively correlates with CD8T cells, which have cancer suppressive effects ( An et al, 2021 ). In hepatocellular carcinoma (HCC), KIF2C can promote epithelial-mesenchymal transition (EMT) for HCC progression ( Mo et al, 2022 ). Through the TGF-1/Smad signaling pathway, KIF2C promotes thyroid cancer proliferation and migration ( Lin et al, 2021 ).…”