Department of Biochemistry and Molecular Medicine and the Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States of America.
PLoS One. 2020 Feb 3;15(2):e0228590. doi: 10.1371/journal.pone.0228590. eCollection 2020.
Aberrant expression of HOXC6 and HOXC4 is commonly detected in prostate cancer. The high expression of these transcription factors is associated with aggressive prostate cancer and can predict cancer recurrence after treatment. Thus, HOXC4 and HOXC6 are clinically relevant biomarkers of aggressive prostate cancer. However, the molecular mechanisms by which these HOXC genes contribute to prostate cancer is not yet understood. To begin to address the role of HOXC4 and HOXC6 in prostate cancer, we performed RNA-seq analyses before and after siRNA-mediated knockdown of HOXC4 and/or HOXC6 and also performed ChIP-seq to identify genomic binding sites for both of these transcription factors. Our studies demonstrate that HOXC4 and HOXC6 co-localize with HOXB13, FOXA1 and AR, three transcription factors previously shown to contribute to the development of prostate cancer. We suggest that the aberrantly upregulated HOXC4 and HOXC6 proteins may compete with HOXB13 for binding sites, thus altering the prostate transcriptome. This competition model may be applicable to many different human cancers that display increased expression of a HOX transcription factor.
HOXC6 和 HOXC4 的异常表达在前列腺癌中通常被检测到。这些转录因子的高表达与侵袭性前列腺癌相关，并可预测治疗后的癌症复发。因此，HOXC4 和 HOXC6 是侵袭性前列腺癌的临床相关生物标志物。然而，这些 HOXC 基因促进前列腺癌的分子机制尚不清楚。为了开始研究 HOXC4 和 HOXC6 在前列腺癌中的作用，我们在使用 siRNA 介导敲低 HOXC4 和/或 HOXC6 之前和之后进行了 RNA-seq 分析，并且还进行了 ChIP-seq 以鉴定这两个转录因子的基因组结合位点。我们的研究表明，HOXC4 和 HOXC6 与 HOXB13、FOXA1 和 AR 共定位，这三个转录因子先前被证明有助于前列腺癌的发展。我们认为，异常上调的 HOXC4 和 HOXC6 蛋白可能与 HOXB13 竞争结合位点，从而改变前列腺转录组。这种竞争模型可能适用于许多不同的人类癌症，这些癌症显示出 HOX 转录因子的表达增加。
Zotero 插件
