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Title

The Role of RNA Helicase DHX9 in Breast Cancer

Date of Award

Spring 5-15-2015

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Molecular Genetics & Genomics)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

DHX9, also known as RNA helicase A (RHA), has been found to be upregulated in various cancers, including breast and lung cancers. Characteristic of members of the DEAD/DEAH-box family of NTP-dependent RNA helicases, DHX9 contains highly conserved amino acid motifs, including the four amino acid residues, Asp-Glu-Ala-Asp/His, for which the family is named after. Well-known members of the DEAD/DEAH-box family of RNA helicases include the translation initiation factor eIF4A (DDX2) and the multi-functional transcription factors p68 (DDX5) and p72 (DDX17). Through their ability to unwind complex secondary and tertiary RNA structures, members of this family have been shown to play important roles in RNA metabolism - ribosome biogenesis, transcription, editing, RNA decay, pre-mRNA splicing, and translation.

Given that DEAD/DEAH-box RNA helicases are key regulators of RNA metabolism, and hence, cellular growth, it comes as no surprise that they are often dysregulated in cancer. In particular, recent whole genome analysis and RNA-Seq studies have revealed that the DHX9 locus is amplified in a significant number of tumor samples from breast cancer patients. This raises the question: Does DHX9 drive or promote oncogenesis? Through knockdown and overexpression studies of DHX9 in various breast cell lines, I demonstrate that DHX9 is required for and is sufficient to drive cellular proliferation through its role in ribosome biogenesis; however, DHX9 is not a bona fide oncogene.

Language

English (en)

Chair and Committee

Jason D Weber

Committee Members

James Skeath, Sergej Djuranovic, Loren Michel, Matthew Walter, Katherine Weilbaecher

Comments

Permanent URL: https://doi.org/10.7936/K7Q81B75

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