Alpha Satellite RNA Levels Are Upregulated in the Blood of Patients with Metastatic Castration-Resistant Prostate Cancer.

Sven Ljubić,Angela Prgomet Sečan,Jure Murgić,Antonio Sermek,Blanka Jakšić,Marin Prpić,Ana Fröbe,Isidoro Feliciello,Đurđica Ugarković

doi:10.3390/genes13020383

Sven Ljubić, Angela Prgomet Sečan + Show 7 more

Open Access

https://doi.org/10.3390/genes13020383

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Abstract

The aberrant overexpression of alpha satellite DNA is characteristic of many human cancers including prostate cancer; however, it is not known whether the change in the alpha satellite RNA amount occurs in the peripheral tissues of cancer patients, such as blood. Here, we analyse the level of intracellular alpha satellite RNA in the whole blood of cancer prostate patients at different stages of disease and compare it with the levels found in healthy controls. Our results reveal a significantly increased level of intracellular alpha satellite RNA in the blood of metastatic cancers patients, particularly those with metastatic castration-resistant prostate cancer relative to controls. In the blood of patients with localised tumour, no significant change relative to the controls was detected. Our results show a link between prostate cancer pathogenesis and blood intracellular alpha satellite RNA levels. We discuss the possible mechanism which could lead to the increased level of blood intracellular alpha satellite RNA at a specific metastatic stage of prostate cancer. Additionally, we analyse the clinically accepted prostate cancer biomarker PSA in all samples and discuss the possibility that alpha satellite RNA can serve as a novel prostate cancer diagnostic blood biomarker.

Highlights

Satellite DNAs are tandemly repeated sequences predominantly located within constitutive heterochromatin which is positioned in thecentromeric and subtelomeric regions of chromosomes
We isolated intracellular RNA from whole blood which was collected from prostate cancer patients belonging to four groups representing different stages of disease: A—representing patients with metastatic hormone-sensitive prostate cancer; B—patients with metastatic castration-resistant cancer; C—patients with localised hormone-sensitive prostate cancer; and D which included patients with newly diagnosed localised prostate cancer before receiving hormone or any other treatment
To measure the level of alpha satellite RNA in the total intracellular RNA isolated from the whole blood of patients from four different groups (A–D) as well as from healthy controls, we used quantitative real-time PCR analysis

Summary

Introduction

Satellite DNAs are tandemly repeated sequences predominantly located within constitutive heterochromatin which is positioned in the (peri)centromeric and subtelomeric regions of chromosomes. Alpha satellite DNA contributes to essential chromosomal functions such as the formation of the centromere/kinetochore as well as of constitutive heterochromatin [2]. Of particular importance is the role of alpha satellite DNA transcripts whose interaction with the enzyme SUV39H1 is necessary for the proper formation and regulation of heterochromatin in the pericentromeric regions [4], and at alpha satellite repeats dispersed within euchromatin [5]. Numerous diseases including cancers can result from deregulated epigenetic mechanisms, which affect the structure of pericentromeric heterochromatin and the expression of sequences located therein. The lower the level of KDM2A expression, the higher pericentromeric heterochromatin transcription and the more severe the tumour grade in prostate cancer [6]

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