Molecular and Cellular Probes (Dec 2023)
KIF2C promotes clear cell renal cell carcinoma progression via activating JAK2/STAT3 signaling pathway
Abstract
Background: Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors that can be highly aggressive. Despite advances in the exploration of its underlying molecular biology, the clinical outcome for advanced ccRCC is still unsatisfied. Recently, more attention was paid to the functions of Kinesin family member 2C (KIF2C) in cancer progression, while the specific function of KIF2C in ccRCC has not been sufficiently elucidated. The present study aims to investigate the role of KIF2C in the progression of ccRCC and reveal potential mechanisms. Methods: Expression of KIF2C in ccRCC tissues and adjacent normal tissue was compared and the association of KIF2C expression level with tumor grade, stage, and metastasis were analyzed using online web tool. Kaplan-Meier survival was performed to detect the association of KIF2C expression and patient’ prognosis. Stably cell lines with KIF2C knockdown or overexpression were constructed by lentivirus infection. CCK-8, colony formation, scratch healing, and transwell invasion assays were carried out to explore the effect of KIF2C knockdown or overexpression on the proliferation, migration, and invasion of ccRCC cells. Gene set enrichment analysis (GSEA) was conducted to reveal signaling pathways associated with KIF2C expression. The effect of KIF2C on JAK2/STAT3 signaling pathway were explored by western blot assay. Results: KIF2C expression was significantly upregulated in ccRCC tissues and was higher with the increase of tumor grade, stage, and metastasis. Higher expression of KIF2C was correlated with worse overall survival and diseases free survival in ccRCC patients. Silence of KIF2C inhibited proliferation, migration, and invasion in ccRCC cells. Conversely, overexpression of KIF2C had the opposite effect. GSEA results showed that JAK/STAT signaling pathway was markedly enriched in KIF2Chigh group. Pearson’ correlation revealed that KIF2C expression was significantly associated with genes in JAK2/STAT3 signaling. Western blot results showed that KIF2C knockdown decreased protein expression of p-JAK2 and p-STAT3, and KIF2C overexpression increased the phosphorylation of JAK2 and STAT3. AG490, a JAK2/STAT3 signaling inhibitor, could partly impair the tumor-promoting effects of KIF2C in ccRCC. Conclusion: KIF2C expression was significantly upregulated in ccRCC and correlated with tumor grade, stage, metastasis, and patients’ prognosis. KIF2C promoted ccRCC progression via activating JAK2/STAT3 signaling pathway, and KIF2C might be a novel target in ccRCC therapy.
