HOXD1 functions as a novel tumor suppressor in kidney renal clear cell carcinoma

Yuanbo Cui1,2, Chunyan Zhang3, Ya Li2

  • 1Department of Translational Medicine Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.

Insights

Homeobox-D (HOXD) genes, including HOXD1, are dysregulated in kidney renal clear cell carcinoma (KIRC). Low HOXD1 expression indicates poor prognosis and suggests HOXD1 acts as a tumor suppressor in KIRC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Kidney renal clear cell carcinoma (KIRC) is a prevalent genitourinary malignancy.
  • The homeobox-D (HOXD) gene cluster's role in KIRC progression is largely uncharacterized.
  • Understanding HOXD gene expression is crucial for identifying KIRC biomarkers.

Purpose of the Study:

  • To investigate the expression patterns and prognostic significance of HOXD genes in KIRC.
  • To elucidate the functional role of HOXD1 in KIRC development and progression.

Main Methods:

  • Comprehensive analysis of HOXD gene expression and survival data using TCGA databases (GEPIA, UALCAN, starBase v3.0, LinkedOmics).
  • Gene Set Enrichment Analysis (GSEA) to identify associated signaling pathways.
  • In vitro loss-of-function and gain-of-function experiments to assess HOXD1's functional impact.

Main Results:

  • HOXD1, HOXD8, and HOXD10 mRNA levels were significantly downregulated in KIRC tissues.
  • Low expression of HOXD1 or HOXD8 correlated with poor overall survival (OS).
  • Downregulated HOXD1, HOXD3, or HOXD4 predicted unfavorable disease-free survival (DFS).
  • HOXD1 downregulation was associated with advanced tumor stages and correlated with OS and DFS.
  • HOXD1 was implicated in cell cycle regulation, TGF-β, and Wnt signaling pathways.
  • HOXD1 inhibited KIRC cell proliferation, cell cycle, and TGF-β signaling.

Conclusions:

  • HOXD1 is frequently downregulated in KIRC and serves as a potential prognostic biomarker.
  • HOXD1 exhibits tumor-suppressive functions by inhibiting cell proliferation and key signaling pathways.
  • Targeting HOXD1 may offer a novel therapeutic strategy for KIRC.

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