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Background <p>Clear cell renal cell carcinoma (ccRCC) is primarily driven by chromosome 3p loss and inactivation of the von Hippel-Lindau (<i>VHL</i>) 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.</p> Methods <p>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.</p> Results <p>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 <i>ARL10</i> in ccRCC tumours and increased circulating miR-1271-5p in patient plasma. Mechanistically, these upregulations resulted from <i>VHL</i> 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 <i>ARL10</i>. Importantly, this regulatory mechanism was specific to kidney cells.</p> Conclusions <p>Coordinated upregulation of miR-1271-5p and <i>ARL10</i> 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.</p>

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Kidney-specific HIF-1α-dependent ARL10/miR-1271-5p overexpression in clear cell renal cell carcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月17日

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  • Patric M. Page,
  • Tania Laperrière,
  • Sonia A. Dastous,
  • Sophie E. Landry,
  • Patrick O. Richard,
  • Michel Pavic,
  • Sandra Turcotte

摘要

Background

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.

Methods

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.

Results

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.

Conclusions

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.