Clear cell renal cell carcinoma (ccRCC) is primarily driven by chromosome 3p loss and inactivation of the von Hippel-Lindau (VHL) gene, which is frequently accompanied by chromosome 5q gain. However, the oncogenic contribution of 5q remains unclear. This study examines how 5q gain affects the expression of microRNAs implicated in ccRCC.
Bioinformatic analyses were conducted to evaluate miRNAs associated with 5q gain and 3p loss. RT-qPCR validation was performed in tumour tissues and patient plasma. Mechanistic investigations integrated open-source ChIP-seq datasets and luciferase reporter assays.
miR-1271-5p overexpression was significantly associated with both 5q gain and 3p loss and strongly correlated with its host gene, ARL10. RT-qPCR confirmed elevated levels of miR-1271-5p and ARL10 in ccRCC tumours and increased circulating miR-1271-5p in patient plasma. Mechanistically, these upregulations resulted from VHL loss and subsequent HIFα stabilisation. ChIP-seq datasets and luciferase assays demonstrated that HIF-1α, but not HIF-2α, directly binds within the intragenic region of ARL10. Importantly, this regulatory mechanism was specific to kidney cells.
Coordinated upregulation of miR-1271-5p and ARL10 reflects key genomic events in ccRCC and is driven by kidney-specific HIF-1a activity. Our findings suggest their promise for early detection and disease monitoring.
British journal of cancer. 2026 Apr 17 [Epub ahead of print]
Patric M Page, Tania Laperrière, Sonia A Dastous, Sophie E Landry, Patrick O Richard, Michel Pavic, Sandra Turcotte
Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, Canada., Department of Urology, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada., Institut de recherche sur le cancer de l'Université de Sherbrooke, Sherbrooke, QC, Canada., Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, Canada. .