Open AccessArticle
Long Non-Coding RNA DUXAP10 Promotes Tumorigenesis and Metastasis in Anaplastic Thyroid Cancer
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Nicole R. DeSouza, Michelle Carnazza, Tara Jarboe, Danielle Quaranto, Kaci Kopec, Anthony J. Centone, Kate Nielsen, Robert Suriano, Augustine Moscatello, Humayun K. Islam, Xiu-Min Li, Jan Geliebter and Raj K. Tiwari
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Abstract
Background: Long non-coding RNAs (lncRNAs) are regulatory molecules that have multifaceted impacts on the carcinogenic molecular landscape—with pathologic consequences when aberrantly expressed. Anaplastic thyroid cancer (ATC) is a rapidly progressing and highly lethal malignancy, with mortality rates approaching 100%. The molecular/transcriptomic signature
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Background: Long non-coding RNAs (lncRNAs) are regulatory molecules that have multifaceted impacts on the carcinogenic molecular landscape—with pathologic consequences when aberrantly expressed. Anaplastic thyroid cancer (ATC) is a rapidly progressing and highly lethal malignancy, with mortality rates approaching 100%. The molecular/transcriptomic signature of ATC has significant gaps in understanding; thus, a comprehensive study of ATC non-coding RNA transcript regulation is necessary.
Results: The lncRNA Double Homeobox A Pseudogene 10 (DUXAP10) was identified in patient genomic datasets as a highly upregulated transcript in ATC vs. normal thyroid tissue. DUXAP10 expression was transcriptionally repressed with CRISPR-interference (CRISPRi), and data supports an extensive role of DUXAP10 in several cancer-promoting phenotypes in ATC, both in vitro and in vivo. Our two DUXAP10-CRISPRi cell lines significantly reduced the rapid growth and metastatic behaviors characteristic of ATC, affecting proliferation, viability, clonogenicity, apoptosis, invasion, migration, tumorigenesis, and metastasis.
Conclusion: Thus, DUXAP10 is a proposed prognostic marker and therapeutic target for ATC disease propagation and progression.
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