Essential role of JunD in cell proliferation is mediated via MYC signaling in prostate cancer cells.

Essential role of JunD in cell proliferation is mediated via MYC signaling in prostate cancer cells.

Cancer Lett. 2019 Feb 11;:

Authors: Elliott B, Millena AC, Matyunina L, Zhang M, Zou J, Wang G, Zhang Q, Bowen N, Eaton V, Webb G, Thompson S, McDonald J, Khan S

Abstract
JunD, a member of the AP-1 family, is essential for cell proliferation in prostate cancer (PCa) cells. We recently demonstrated that JunD knock-down (KD) in PCa cells results in cell cycle arrest in G1-phase concomitant with a decrease in cyclin D1, Ki67, and c-MYC, but an increase in p21 levels. Furthermore, the over-expression of JunD significantly increased proliferation suggesting JunD regulation of genes required for cell cycle progression. Here, employing gene expression profiling, quantitative proteomics, and validation approaches, we demonstrate that JunD KD is associated with distinct gene and protein expression patterns. Comparative integrative analysis by Ingenuity Pathway Analysis (IPA) identified 1) cell cycle control/regulation as the top canonical pathway whose members exhibited a significant decrease in their expression following JunD KD including PRDX3, PEA15, KIF2C, and CDK2, and 2) JunD dependent genes are associated with cell proliferation, with MYC as the key downstream regulator. Conversely, JunD over-expression induced the expression of above genes including c-MYC. We conclude that JunD is a key regulator of cell cycle progression and inhibiting its target genes may be an effective approach to block prostate carcinogenesis.

PMID: 30763715 [PubMed - as supplied by publisher]

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