miR-148a, miR-152 and miR-200b promote prostate cancer metastasis by targeting DNMT1 and PTEN expression.

Autor: Gurbuz V; Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, Ankara 06510, Turkey., Sozen S; Department of Urology, Faculty of Medicine, Gazi University, Ankara 06510, Turkey., Bilen CY; Department of Urology, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey., Konac E; Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, Ankara 06510, Turkey.
Jazyk: angličtina
Zdroj: Oncology letters [Oncol Lett] 2021 Nov; Vol. 22 (5), pp. 805. Date of Electronic Publication: 2021 Sep 23.
DOI: 10.3892/ol.2021.13066
Abstrakt: MicroRNAs (miRs) modulate the expression of target genes in the signal pathway on transcriptome level. The present study investigated the 'epigenetic-based miRNA (epi-miRNA)-mRNA' regulatory network of miR-34b, miR-34c, miR-148a, miR-152, miR-200a and miR-200b epi-miRNAs and their target genes, DNA methyltransferase (DNMT1, 3a and 3b), phosphate and tensin homolog (PTEN) and NK3 Homeobox 1 (NKX3.1), in prostate cancer (PCa) using reverse transcription-quantitative PCR. The expression level of NKX3.1 were not significantly different between the PCa, Met-PCa and control groups. However, in the PCa and Met-PCa groups, the expression level of DNMT1 was upregulated, while DNMT3a, DNMT3b and PTEN were downregulated. Overexpression of DNMT1 (~5 and ~6-fold increase in the PCa and Met-PCa groups respectively) was accompanied by a decreased expression in PTEN, indicating a potential negative association. Both groups indicated that a high level of DNMT1 is associated with the aggressiveness of cancer, and there is a a directly proportional relationship between this gene and PSA, GS and TNM staging. A significant ~2 to ~5-fold decrease in the expression levels of DNMT3a and DNMT3b was found in both groups. In the PCa group, significant associations were identified between miR-34b and DNMT1/DNMT3b; between miR-34c/miR-148a and all target genes; between miR-152 and DNMT1/DNMT3b and PTEN; and between miR-200a/b and DNMT1. In the Met-PCa group, miR-148a, miR-152 and miR-200b exhibited a significant association with all target genes. A significant negative association was identified between PTEN and DNMT1 in the Met-PCa group. It was also revealed that that miR-148a, miR-152 and miR-200b increased the expression of DNMT1 and suppressed PTEN. Furthermore, the 'epi-miRNA-mRNA' bidirectional feedback loop was emphasised and the methylation pattern in PCa anti-cancer therapeutics was highlighted.
Competing Interests: The authors declare that they have no competing interests
(Copyright: © Gurbuz et al.)
Databáze: MEDLINE
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