MicroRNA-like snoRNA-Derived RNAs (sdRNAs) Promote Castration-Resistant Prostate Cancer

Alexander B. Coley; Ashlyn N. Stahly; Mohan V. Kasukurthi; Addison A. Barchie; Sam B. Hutcheson; Dominika Houserova; Yulong Huang; Brianna C. Watters; Valeria M. King; Meghan A. Dean; Justin T. Roberts; Jeffrey D. DeMeis; Krisha V. Amin; Cameron H. McInnis; Noel L. Godang; Ryan M. Wright; David F. Haider; Neha B. Piracha; Cana L. Brown; Zohaib M. Ijaz; Shengyu Li; Yaguang Xi; Oliver G. McDonald; Jingshan Huang; Glen M. Borchert

doi:10.3390/cells11081302

Cells (Apr 2022)

MicroRNA-like snoRNA-Derived RNAs (sdRNAs) Promote Castration-Resistant Prostate Cancer

Alexander B. Coley,
Ashlyn N. Stahly,
Mohan V. Kasukurthi,
Addison A. Barchie,
Sam B. Hutcheson,
Dominika Houserova,
Yulong Huang,
Brianna C. Watters,
Valeria M. King,
Meghan A. Dean,
Justin T. Roberts,
Jeffrey D. DeMeis,
Krisha V. Amin,
Cameron H. McInnis,
Noel L. Godang,
Ryan M. Wright,
David F. Haider,
Neha B. Piracha,
Cana L. Brown,
Zohaib M. Ijaz,
Shengyu Li,
Yaguang Xi,
Oliver G. McDonald,
Jingshan Huang,
Glen M. Borchert

Affiliations

Alexander B. Coley: Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA
Ashlyn N. Stahly: Medical Scientist Training Program, University of Colorado School of Medicine, Aurora, CO 80045, USA
Mohan V. Kasukurthi: School of Computing, University of South Alabama, Mobile, AL 36608, USA
Addison A. Barchie: Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA
Sam B. Hutcheson: Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA
Dominika Houserova: Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA
Yulong Huang: Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA
Brianna C. Watters: Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA
Valeria M. King: Department of Biology, University of South Alabama, Mobile, AL 36608, USA
Meghan A. Dean: Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA
Justin T. Roberts: Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA
Jeffrey D. DeMeis: Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA
Krisha V. Amin: Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA
Cameron H. McInnis: Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA
Noel L. Godang: Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA
Ryan M. Wright: Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA
David F. Haider: Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA
Neha B. Piracha: Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA
Cana L. Brown: Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA
Zohaib M. Ijaz: Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA
Shengyu Li: School of Computing, University of South Alabama, Mobile, AL 36608, USA
Yaguang Xi: Department of Genetics, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
Oliver G. McDonald: Department of Pathology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33146, USA
Jingshan Huang: School of Computing, University of South Alabama, Mobile, AL 36608, USA
Glen M. Borchert: Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36608, USA

DOI: https://doi.org/10.3390/cells11081302
Journal volume & issue: Vol. 11, no. 8
p. 1302

Abstract

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We have identified 38 specifically excised, differentially expressed snoRNA fragments (sdRNAs) in TCGA prostate cancer (PCa) patient samples as compared to normal prostate controls. SnoRNA-derived fragments sdRNA-D19b and -A24 emerged among the most differentially expressed and were selected for further experimentation. We found that the overexpression of either sdRNA significantly increased PC3 (a well-established model of castration-resistant prostate cancer (CRPC)) cell proliferation, and that sdRNA-D19b overexpression also markedly increased the rate of PC3 cell migration. In addition, both sdRNAs provided drug-specific resistances with sdRNA-D19b levels correlating with paclitaxel resistance and sdRNA-24A conferring dasatinib resistance. In silico and in vitro analyses revealed that two established PCa tumor suppressor genes, CD44 and CDK12, represent targets for sdRNA-D19b and sdRNA-A24, respectively. This outlines a biologically coherent mechanism by which sdRNAs downregulate tumor suppressors in AR-PCa to enhance proliferative and metastatic capabilities and to encourage chemotherapeutic resistance. Aggressive proliferation, rampant metastasis, and recalcitrance to chemotherapy are core characteristics of CRPC that synergize to produce a pathology that ranks second in cancer-related deaths for men. This study defines sdRNA-D19b and -A24 as contributors to AR-PCa, potentially providing novel biomarkers and therapeutic targets of use in PCa clinical intervention.

Published in Cells

ISSN: 2073-4409 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General): Cytology
Website: https://www.mdpi.com/journal/cells

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