N6-methyladenosine contributes to cellular phenotype in a genetically-defined model of breast cancer progression

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dc.contributor.authorFry, Nate J.
dc.contributor.authorLaw, B. A.
dc.contributor.authorIlkayeva, O. R.
dc.contributor.authorHolley, C. L.
dc.contributor.authorMansfield, Kyle D.
dc.contributor.authorCarraway, Kristen R.
dc.date.accessioned2019-06-20T19:13:51Z
dc.date.available2019-06-20T19:13:51Z
dc.date.issued2018-07-27
dc.description.abstractThe mRNA modification N6-methyladenosine (m6A) is involved in many post-transcriptional regulatory processes including mRNA stability and translational efficiency. However, it is also imperative to correlate these processes with phenotypic outputs during cancer progression. Here we report that m6A levels are significantly decreased in genetically-defined immortalized and oncogenically-transformed human mammary epithelial cells (HMECs), as compared with their primary cell predecessor. Furthermore, the m6A methyltransferase (METTL3) is decreased and the demethylase (ALKBH5) is increased in the immortalized and transformed cell lines, providing a possible mechanism for this basal change in m6A levels. Although the immortalized and transformed cells showed lower m6A levels than their primary parental cell line, overexpression of METTL3 and METTL14, or ALKBH5 knockdown to increase m6A levels in transformed cells increased proliferation and migration. Remarkably, these treatments had little effect on the immortalized cells. Together, these results suggest that m6A modification may be downregulated in immortalized cells as a brake against malignant progression. Finally, we found that m6A levels in the immortalized and transformed cells increased in response to hypoxia without corresponding changes in METTL3, METTL14 or ALKBH5 expression, suggesting a novel pathway for regulation of m6A levels under stress.en_US
dc.description.sponsorshipECU Open Access Publishing Support Funden_US
dc.identifier.citationFry, N.J ., Law, B. A., Ilkayeva, O.R., Carraway, K. R., Holley, C.L., & Mansfield, K.D. N6-methyladenosine contributes to cellular phenotype in a genetically-defined model of breast cancer progression. Oncotarget, 9(58): 31231-31243. doi: 10.18632/oncotarget.25782.en_US
dc.identifier.doi10.18632/oncotarget.25782
dc.identifier.otherPMC6101291
dc.identifier.pmid30131850en_US
dc.identifier.urihttp://hdl.handle.net/10342/7356
dc.language.isoen_USen_US
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/30131850en_US
dc.subjectN6-methyladenosineen_US
dc.subjectRNA modificationen_US
dc.subjectbreast canceren_US
dc.subjecthypoxiaen_US
dc.subjecttransformationen_US
dc.titleN6-methyladenosine contributes to cellular phenotype in a genetically-defined model of breast cancer progressionen_US
dc.typeArticleen_US
ecu.journal.issue58en_US
ecu.journal.nameOncotargeten_US
ecu.journal.pages31231-31243en_US
ecu.journal.volume9en_US

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