Transcriptomic Profiling Analysis of Castration-Resistant Prostate Cancer Cell Lines Treated with Chronic Intermittent Hypoxia

Abstract

Castration-resistant prostate cancer (CRPC) is still a major concern in men’s health, with 375,000 cancer deaths annually. Hypoxia, which is a marked characteristic of advanced solid tumors, has been suggested to induce prostate cancer towards CRPC, metastasis and treatment resistance. To evaluate the effect of hypoxia on prostate cancer, two and five cycles of hypoxia and reoxygenation were administered using 22Rv1 cell lines and denominated as 22Rv1-CI and 22Rv1-PCI, respectively. Cancer cell migration was promoted in 22Rv1-CI compared to controls, and the expression of COL13A1 was significantly up-regulated in 22Rv1-CI according to differentially expressed gene analysis of RNA sequencing among groups. Cancer cell migration was impeded in a wound healing assay after transfecting si-COL13A1. Moreover, the expression of COL13A1 was also higher in the cell line originating from bone metastatic prostate cancer compared to other cell lines. Using the open database GEO, we also confirmed that the expression of COL13A1 was higher in bone metastatic prostate cancer tissue than in localized prostate cancer tissue in patients. Therefore, COL13A1 may be closely related to the bony metastasis of prostate cancer, and our findings may provide valuable information on the pathophysiology of the metastatic niche induced by hypoxia in patients with CRPC.

Exploring the tumor genomic landscape of aggressive prostate cancer by whole‐genome sequencing of tissue or liquid biopsies

“…8,10,52 To our knowledge, COL13A1, KCNH3, and SENP3 have not been reported in this context previously. However, COL13A1 has been reported as upregulated in PC patients with bone metastases compared with primary PC patients 53 and high expression of KCNH3 54 and SENP3 55 has been linked to poor prognosis in ovarian and breast cancer, respectively, thus suggesting that these genes may also constitute novel potential driver genes in aggressive PC. This should be investigated in future studies comprising more patients.…”