<i>MiR137</i>is an androgen regulated repressor of an extended network of transcriptional coregulators

Nilsson, Elise; Laursen, Kristian B.; Whitchurch, Jonathan B.; McWilliam, Andrew S.; Ødum, Niels; Persson, Jenny L.; Heery, David M.; Gudas, Lorraine J.; Mongan, Nigel P.

doi:10.18632/oncotarget.5958

Cited by 51 publications

(51 citation statements)

References 99 publications

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“…However, this notion requires further validation. Our data regarding regulation of KDM5B expression by miR-137 in PTEN null conditions is in clear agreement with earlier studies (28,29). The oncogenic roles of KDM5B are now well explored in prostate cancer; however, information regarding its regulation at both transcriptional and translational levels still remains scarce.…”

Section: Discussionsupporting

confidence: 92%

AKT Inhibition Modulates H3K4 Demethylase Levels in PTEN-Null Prostate Cancer

Khan

Hamid

Rath

et al. 2019

Molecular Cancer Therapeutics

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Hyperactivated AKT kinase due to loss of its negative regulator PTEN influences many aspects of cancer biology, including chromatin. AKT primarily regulates acetyl-CoA production and phosphorylates many histone-modulating enzymes, resulting in their activation or inhibition. Therefore, understanding the therapeutic impact of AKT inhibition on chromatin-related events is essential. Here, we report that AKT inhibition in prostate-specific PTEN knockout mice significantly induces di-and trimethylation of H3K4 with concomitant reduction in H3K9 acetylation. Mechanistically, we observed that AKT inhibition reduces expression of the H3K4 methylation-specific histone demethylases KDM5 family, especially KDM5B expression at transcriptional levels. Furthermore, we observed that AKT negatively regulates miR-137 levels, which transcriptionally represses KDM5B expression. Overexpression of miR-137 significantly reduced KDM5B and increased H3K4 methylation levels but failed to change AKT phosphorylation. Overall, we observed that AKT transcriptionally regulates KDM5B mainly via repression of miR-137. Our data identify a mechanism by which AKT kinase modulates the prostate cancer epigenome through regulating H3K4 methylation. Additional studies on AKT inhibition-mediated induction of H3K4 methylation will help in designing strategies to enhance the therapeutic efficacy of PI3K/AKT inhibitors.

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Section: Discussionsupporting

confidence: 92%

AKT Inhibition Modulates H3K4 Demethylase Levels in PTEN-Null Prostate Cancer

Khan

Hamid

Rath

et al. 2019

Molecular Cancer Therapeutics

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“…In the present study, we found that hsa-miR-137 is upregulated in young PCa, while in the literature has been reported downregulated and associated with recurrence following prostatectomy [52]. hsa-miR-137 has a function as an androgen regulated suppressor of androgen signaling by modulating expression of an extended network of transcriptional coregulators [53].…”

Section: Discussionsupporting

confidence: 46%

microRNA Expression Profiling in Young Prostate Cancer Patients

et al. 2020

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MicroRNAs (miRNAs) are small, non-coding RNA molecules with multiple roles in many biological processes. Few studies have shown the molecular characteristics in younger prostate cancer (PCa) patients. In this study, we performed miRNA profiling in young PCa (EO-PCa) cases compared with PCa arising in older men (LO-PCa). Experimental Design: Formalin-fixed, paraffin embedded tissue was used. miRNA was extracted for PCR array and NanoString methods. Relative miRNAs expression levels were obtained by comparing young vs older men, and young PCa tumor samples vs normal epithelium. Results: miRNA profiling showed a different expression pattern in PCa arising in younger men, and young PCa tumoral and its normal counterpart. Nine miRNAs showed differences in the expression compared to LO-PCa. Fourteen miRNAs were significantly up-regulated young PCa tumoral tissue compared to normal counterpart. The higher expression of miR-600 and miR-137 were associated with high Gleason score, extraprostatic extension and lymphatic invasion. Conclusion: These results suggest that PCa in younger patients has a different expression profile compared to normal tissue and PCa arising in older man. Differentially expressed miRNAs provide insights of molecular mechanisms involve in this PCa subtype.

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“…Androgens are essential for normal development of the male gender, and spermatogenesis (Nilsson et al, 2015). Androgen activity is mediated by the androgen receptor (AR), a member of the steroid receptor superfamily (Davis-Dao et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Impact of CAG repeat length in the androgen receptor gene on male infertility – a meta-analysis

Xiao

Lan

Lin

et al. 2016

Reproductive BioMedicine Online

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CAG repeats are polymorphic nucleotide repeats present in the androgen receptor gene. Many studies have estimated the association between CAG repeat length and male infertility, but the conclusions are controversial. Previous meta-analyses have come to different conclusions; however, new studies have been published. An updated meta-analysis was conducted. PubMed, CBM, CNKI and Web of Science databases were systematically searched for studies published from 1 January 2000 to 1 October 2015. Case-control studies on the association between CAG repeat length and male infertility using appropriate methodology were included. Forty studies were selected, including 3858 cases and 3161 controls. Results showed statistically significantly longer CAG repeat length among cases compared with controls (SMD = 0.14; 95% CI, 0.02-0.26). Shorter repeat length was associated with a lower risk of male infertility compared with a longer repeat length in the overall analysis (OR = 0.79, 95% CI: 0.66-0.95). Moreover, CAG repeat length was associated with male infertility in Caucasian populations, but not Asian or Egyptian populations. Subgroup analysis revealed no significant difference in German populations, but CAG repeat length was associated with male infertility in China and the USA. There were no significant differences between cases and controls in azoospermia and severe oligozoospermia.

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MiR137is an androgen regulated repressor of an extended network of transcriptional coregulators

Cited by 51 publications

References 99 publications

AKT Inhibition Modulates H3K4 Demethylase Levels in PTEN-Null Prostate Cancer

AKT Inhibition Modulates H3K4 Demethylase Levels in PTEN-Null Prostate Cancer

microRNA Expression Profiling in Young Prostate Cancer Patients

Impact of CAG repeat length in the androgen receptor gene on male infertility – a meta-analysis

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