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

Abstract

Simple SummaryProstate cancer is the second most frequently diagnosed cancer and the fifth cause of cancer mortality among men. Although localized and confined tumors are relatively curable, patients with advanced metastatic prostate cancer are still problematic. Hypoxia, which is a marked characteristic of advanced solid tumors, has been suggested to induce the progression of prostate cancer. This study aimed to evaluate the impact of chronic intermittent hypoxia on a castration-resistant prostate cancer cell line in inducing cancer progression using RNA sequencing analysis. Through RNA sequencing analysis, we prove that COL13A1, which is a key factor for the progression of metastasis, is closely related to metastatic prostate cancer. These results suggest that our findings indicate a novel strategy for the clinical management of mCRPC.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.