Renal papillary cell carcinoma (pRCC) is a prevalent subtype of kidney cancer with unclear pathogenesis and limited therapeutic options. The Anillin protein plays critical roles in cell division and cytoskeleton organization; it has not been fully explored in pRCC.
Clinical samples were collected, human renal fibroblasts and pRCC cell lines were cultured, and cancer-associated fibroblasts (CAFs) ECM were established. In vitro genetic manipulations of ANLN and RBM15B were conducted. CCK-8, EdU staining, wound healing assay, and Transwell assays were employed to investigate pRCC cell behaviors. Molecular mechanisms were investigated via RT-qPCR, Western blotting, RNA immunoprecipitation, MeRIP-qPCR, chromatin immunoprecipitation, and mRNA stability assays. Lactate levels and histone lactylation modifications were analyzed.
ANLN expression was upregulated in pRCC tissues and cell lines; its expression levels correlated with tumor progression. Knockdown of ANLN inhibited malignant progression of pRCC cells. CAFs promoted the malignant progression of pRCC cells and upregulated ANLN expression through lactate. Mechanistically, lactate enhanced mRNA stability of ANLN in an m6A-dependent manner, accelerating the malignant progression of pRCC cells. Notably, lactate enhanced RBM15B expression by promoting histone lactylation of RBM15B, which in turn promoted ANLN expression through m6A modification. Knockdown of RBM15B abolished CAFs-induced ANLN upregulation, suppressing pRCC tumor progression.
CAFs drove pRCC oncogenesis through epigenetic reprogramming of RBM15B via histone lactylation, which subsequently modulated ANLN expression in an m6A-dependent manner. This study offers novel insights into the role of ANLN in pRCC and identifies potential therapeutic targets for this cancer subtype.
International journal of urology : official journal of the Japanese Urological Association. 2026 Jun [Epub]
Jiawei Shen, Peng Yu, Wenfa Mo, Junming Li, Haixiao Fu, Xuebao Xiang
Department of Urology, The First Affiliated Hospital of Guilin Medical University, Guilin, People's Republic of China.