NUF2-HMGA2 axis drives cell proliferation, migration, and invasion in clear cell renal cell carcinoma

The relatively poor sensitivity of clear cell renal cell carcinoma (ccRCC) to conventional chemotherapy and radiotherapy makes its treatment challenging. The Ndc80 kinetochore complex component (NUF2) is involved in the development and progression of several cancers. However, its role in ccRCC remains unclear. In an effort to identify novel treatment targets and prognostic markers for ccRCC, we investigated the role of NUF2 in ccRCC progression. We found that the expression of NUF2 was increased in ccRCC tissues and cells, and the elevated NUF2 levels were significantly associated with worse clinicopathological parameters and shorter survival. In addition, NUF2 was an independent prognostic biomarker for ccRCC. Knocking down NUF2 expression affected the proliferation, migration, and invasion of ccRCC cells and the expression of epithelial–mesenchymal transition (EMT)-related markers. Moreover, RNA sequencing and in vitro experiments identified the oncogene high-mobility group AT-hook 2 (HMGA2) as the target factor regulated by NUF2 in ccRCC. Restoring HMGA2 levels ameliorated the inhibitory effects of NUF2 depletion on cell proliferative, migratory, and invasive capacities and recovered the expression of EMT-related markers to basal levels.These results suggest that NUF2 promotes proliferation, migration, and invasion of ccRCC cells, at least partly by regulating HMGA2, and that the NUF2-HMGA2 axis could be an ideal therapeutic target and a promising prognostic indicator for ccRCC. mRNA profiles of 769-P and ACHN cells after transfecting with siRNA-NUF2 for 48 h.