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RNA-Seq and Ribo-Seq analysis of contol and METTL3 inducible shRNA LNCaP lines with and without doxycycline induction

ABSTRACT: Genomic and transcriptomic alterations are insufficient to explain the variance in protein expression seen in cancer. Recent evidence has highlighted the role of N6-methyladenosine (m6A) in the regulation of mRNA expression, stability and translation, supporting a potential role for post-transcriptional regulation mediated by m6A in cancer. Here we explore prostate cancer as an exemplar cancer and generate the first prostate m6A maps, and further examined how low levels of N6-adenosine-methyltransferase (METTL3) associates with advanced prostate cancer and results in altered expression at the level of transcription, translation, and protein. In particular extracellular matrix proteins have a high number of m6A sites and show significant changes in expression with METTL3 knock-down. We also discovered the upregulation of a hepatocyte nuclear factor-driven gene signature that is associated with therapy resistance in prostate cancer. Significantly, METTL3 knock-down rendered the cells resistant to androgen receptor antagonists, implicating changes in m6A as a mechanism for therapy resistance in metastatic prostate cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE161301 | GEO | 2021/06/07

REPOSITORIES: GEO

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Mapping of m6A and Its Regulatory Targets in Prostate Cancer Reveals a METTL3-low Induction of Therapy Resistance

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2021-06-07 | PXD022348 | Pride

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