TPX2 promotes papillary renal cell carcinoma progression by forming a ceRNA with LINC00894.
PURPOSE: Papillary renal cell carcinoma (pRCC), particularly type 2, is associated with a poor prognosis. This study aimed to identify molecular mechanisms underlying pRCC progression and explore potential therapeutic targets to improve patient outcomes. METHODS: TPX2 expression was analyzed in tumor samples from patients with type 2 pRCC. In vitro experiments were conducted to assess the effects of TPX2 and LINC00894 knockdown and overexpression on the proliferation and migration of Caki-2 and ACHN cells. Immunohistochemical analysis of tissue microarrays was performed to evaluate the associations between TPX2 expression and clinicopathological characteristics in type 2 pRCC patients. RESULTS: Elevated TPX2 expression was significantly associated with a worse prognosis in type 2 pRCC patients and served as an independent risk factor for overall survival. Knockdown of TPX2 in Caki-2 and ACHN cells significantly reduced cell proliferation and migration. Additionally, LINC00894 was highly expressed in type 2 pRCC and correlated with poor prognosis. Mechanistically, miR-660-5p targeted the TPX2 3' UTR, promoting TPX2 degradation, while LINC00894 competitively bound to miR-660-5p, protecting TPX2 from miRNA-mediated degradation and exerting a pro-oncogenic effect. Immunohistochemical analysis revealed significant correlations between TPX2 expression and clinicopathological features, including tumor thrombus volume, tumor diameter, pathological TNM stage, and Fuhrman grade. CONCLUSION: This study underscores the critical role of TPX2 in type 2 pRCC progression and highlights its potential as a prognostic biomarker and therapeutic target. The TPX2/LINC00894/miR-660-5p regulatory axis provides novel insights into the molecular mechanisms driving pRCC and offers a promising avenue for improving patient prognosis.