American Association for Cancer Research
Browse
15417786mcr200705-sup-249271_3_supp_6911013_q7b37b.xlsx (11.76 kB)

Supplementary Table 4 from Loss of 9p21 Regulatory Hub Promotes Kidney Cancer Progression by Upregulating HOXB13

Download (11.76 kB)
dataset
posted on 2023-04-03, 19:50 authored by Maria Francesca Baietti, Peihua Zhao, Jonathan Crowther, Raj Nayan Sewduth, Linde De Troyer, Maria Debiec-Rychter, Anna A. Sablina

Overlap HOXB13 targets

Funding

ERC

Research Foundation Flanders

History

ARTICLE ABSTRACT

Loss of chromosome 9p21 is observed in one-thirds of clear-cell renal cell carcinoma (ccRCC) and is associated with poorer patient survival. Unexpectedly, 9p21 LOH does not lead to decreased expression of the 9p21 tumor suppressor genes, CDKN2A and CDKN2B, suggesting alternative mechanisms of 9p-mediated tumorigenesis. Concordantly, CRISPR-mediated 9p21 deletion promotes growth of immortalized human embryonic kidney epithelial cells independently of the CDKN2A/B pathway inactivation. The 9p21 locus has a highly accessible chromatin structure, suggesting that 9p21 loss might contribute to kidney cancer progression by dysregulating genes distal to the 9p21 locus. We identified several 9p21 regulatory hubs by assessing which of the 9p21-interacting genes are dysregulated in 9p21-deleted kidney cells and ccRCCs. By focusing on the analysis of the homeobox gene 13 (HOXB13) locus, we found that 9p21 loss relieves the HOXB13 locus, decreasing HOXB13 methylation and promoting its expression. Upregulation of HOXB13 facilitates cell growth and is associated with poorer survival of patients with ccRCC. The results of our study propose a novel tumor suppressive mechanism on the basis of coordinated expression of physically associated genes, providing a better understanding of the role of chromosomal deletions in cancer.