Epigenetic Regulation of SOX2 Gene in Human Prostate Cancer and Prostate Cancer Stem Cells

Abstract

Pluripotency-associated transcription factors such as SOX2, OCT4, NANOG AND KLF4 have been functionally associated with the maintenance and induction of embryonic stem cells. Upregulated expression of these transcription factors predominantly SOX2 has been reported in different types of cancer including prostate cancer (PC). PC is one of the most commonly diagnosed cancer in men. Globally, it is the 6th leading cause of cancer deaths in men. SOX2 affects the PC formation positively. SOX2 has a prominent role in the maintenance of prostate cancer stem cells (PCSCs) and is involved in PC recurrence. Recent advances have shown that, the aberrant expression of SOX2 is the outcome of deregulated epigenetic modifications like DNA methylation and histone protein posttranslational modifications. In this work, we investigated the regulation of SOX2 gene in PC progression and PCSC development. Studies have shown that tumor spheres contain higher population of cancer stem-like cells. So, we developed prostatospheres by hanging drop method and their stem cells properties were validated through checking expression of various stem cell markers like CD133, CD44 etc. Epigenetic profile analysis was performed for SOX2 in prostatospheres in comparison to original PC cells. Alteration in the expression of the SOX2 and its epigenetic status in these PCSCs were investigated by comparing with the PC cells through different types of drug treatments.