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The Cao Lab is conducting research on the identification of PcG protein histone methyltransferase EZH2 as a biomarker for aggressive breast and prostate cancers; characterization of EZH2 as an oncogene in breast and prostate cancer; discovery of genomic loss of miR-101 in breast and prostate cancer and the upregulation of EZH2 by miR-101 in cancer; and coordinated regulation between Polycomb repressive complexes 1 and 2 in breast and prostate cancer progression.

The Cao Lab's work has demonstrated EZH2 and BMI1 as valuable therapeutic targets in cancer; several pharmaceutical companies are now developing EZH2- or BMI1- specific inhibitors for cancer therapy.

Recent Work

 EZH2 Represses PARP1 Activity

By methylating the lysines of PARP1, EZH2 acts as a PARP1 co-factor to recruit PARP1 to genomic loci during the DNA damage response in advanced prostate and breast cancer. We are determining if overexpression of EZH2 and PARP1 will promote cancer progression, and inhibition of both EZH2 and PARP1 will benefit prostate cancer and breast cancer patients.

 Role of Androgen Receptor in the Treatment of Prostate Cancer

Long non-coding RNAs (lncRNAs) are a class of ribonucleic acids with 200 nucleotides longer in size that cannot be translated into proteins, and they have been shown to play important roles in cancer development and progression. Androgen receptor (AR) specifically has a critical role in all stages of prostate cancer; thus, identifying new molecular mechanisms underlying aberrant AR activation by lncRNAs holds great promise to improve the treatment of castration-resistant prostate cancer.

 Investigating ZCCHC7, Zinc Finger CCHC Domain-containing Protein 7

In our previous analysis of H3K27me3 occupation changes in cancer cells, we identified ZCCHC7 – Zinc finger CCHC domain-containing protein 7 – as a promising potent oncogene controlled by H3K27me3 level in prostate cancer with significant, poor overall survival rate. We hypothesize that deletion of ZCCHC7 will suppress tumorigenesis and progression of this malignant cancer. Identifying the critical roles of ZCCHC7 and its downstream RNA processing pathways are essential for improving the preventive and therapeutic interventions of this fatal disease.

 Characterizing Functions of Novel BMI1-regulated lncRNAs and BMI1-binding lncRNAs in Prostate Cancer

Long non-coding RNAs (lncRNAs) are a class of RNAs that are longer than 200 nucleotides and could not be translated to proteins or could only be translated to oligo-peptides. They have been implicated in diverse physiological and pathological processes, such as epigenetic control of gene expression, chromatin organization, genomic imprinting, immune regulation, cell differentiation and development, viral pathogenesis and oncogenesis. LncRNAs are highly deregulated in cancer, and it is believed that lncRNAs represent a class of cancer biomarkers and therapeutic targets whose potential has not been fully explored. Several studies have shown that lncRNAs can bind to PRC1. However, the nature of PRC1 transcriptional regulation of lncRNAs and how lncRNAs modify the function of PRC1 is largely unknown. We are interested in investigating the novel functions of BMI1-associated lncRNAs in prostate cancer progression, and exploring the potential to target BMI1-binding or regulated lncRNAs in the pre-clinical and clinical setting for castration-resistant prostate cancer treatment.