Regulation and Methylation of Tumor Suppressor MiR-124 by Androgen Receptor in Prostate Cancer Cells

Chu, Mingliang; Chang, Yunli; Guo, Yanjing; Wang, Naitao; Cui, Jian; Gao, Wei‐Qiang

doi:10.1371/journal.pone.0116197

Cited by 24 publications

(16 citation statements)

References 28 publications

(40 reference statements)

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“…Thus far, several miRNAs are previously reported to be dysregulated in liver cancer, including miR-21, miR-122, miR-181b, miR-338, and miR-491 (12)(13)(14)(15)(16), which are all closely associated with the migration and metastasis of liver cancer. miR-124a functions as a tumour suppressor in osteosarcoma, endometrial carcinoma, prostate cancer, and glioblastoma (17)(18)(19)(20). It is also downregulated in liver cancer tissues (21).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-124a inhibits cell proliferation and migration in liver cancer by regulating interleukin-11

Wang

Lin

et al. 2017

Mol Med Report

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Liver cancer is the sixth most common malignant tumour and ranks in the top three cancers with regard to mortality due to metastasis and postsurgical recurrence. It is significant to understand the mechanisms underlying liver cancer for diagnosis and treatment. Cumulative evidence suggests that the abnormal regulation of microRNAs (miRNAs/miRs) may contribute to the development and metastasis of cancer. miR‑124a acts as a tumour suppressor in osteosarcoma, endometrial carcinoma, prostate cancer, and glioblastoma. However, the effects of miR‑124a in liver cancer and its biological mechanism are not fully understood. It has been demonstrated that miR‑124a is downregulated and interleukin (IL)‑11 is upregulated in the liver cancer tissues. In the present study, miR‑124a upregulation inhibited cell proliferation, migration and promoted cell apoptosis. Through a dual‑luciferase reporter assay, it was verified that IL‑11 is a direct target of miR‑124a. Furthermore, the overexpression of miR‑124a repressed the secretion of IL‑11 from hepatoma cells. Finally, it was identified that mimics of miR‑124a increased the expression of tissue inhibitor of matrix metalloproteinase‑2 (TIMP‑2) and Caspase‑3 and decreased the expression levels of matrix metalloproteinase 2 (MMP2), MMP9, B‑cell lymphoma 2, signal transducer and activator of transcription 3 (STAT3), and phosphorylated‑STAT3. In conclusion, the results indicated that miR‑124a has an important role as a tumour suppressor gene by targeting IL‑11. These findings may provide novel insights for clinical treatments to prevent the development of liver cancer.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-124a inhibits cell proliferation and migration in liver cancer by regulating interleukin-11

Wang

Lin

et al. 2017

Mol Med Report

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“…Alterations in miR promoter DNA methylation levels have been demonstrated to modulate the abundance of miRs. 26,27 Interestingly, in multiple tumors, including hepatocellular carcinoma, 28 stomach adenocarcinoma, 29 and prostate cancer, 30 it has been shown that miR-124 levels rely strongly on the DNA methylation of its promoter. Downregulation of miR-124 in these tumors promoted their metastasis and/or development.…”

Section: Introductionmentioning

confidence: 99%

Cocaine-mediated downregulation of microglial miR-124 expression involves promoter DNA methylation

et al. 2016

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Neuroinflammation plays a critical role in the development of reward-related behavior in cocaine self-administration rodents. Cocaine, one of most commonly abused drugs, has been shown to activate microglia both in vitro and in vivo. Detailed molecular mechanisms underlying cocaine-mediated microglial activation remain poorly understood. microRNAs (miRs) belonging to a class of small noncoding RNA superfamily have been shown to modulate the activation status of microglia. miR-124, one of the microglia-enriched miRs, functions as an anti-inflammatory regulator that maintains microglia in a quiescent state. To date, the possible effects of cocaine on microglial miR-124 levels and the associated underlying mechanisms have not been explored. In the current study, we demonstrated that cocaine exposure decreased miR-124 levels in both BV-2 cells and rat primary microglia. These findings were further validated in vivo, wherein we demonstrated decreased abundance of miR-124 in purified microglia isolated from cocaine-administered mice brains compared with cells from saline administered animals. Molecular mechanisms underlying these effects involved cocaine-mediated increased mRNA and protein expression of DNMTs in microglia. Consistently, cocaine substantially increased promoter DNA methylation levels of miR-124 precursors (pri-miR-124-1 and -2), but not that of pri-miR-124-3, both in vitro and in vivo. In summary, our findings demonstrated that cocaine exposure increased DNA methylation of miR-124 promoter resulting into its downregulation, which, in turn, led to microglial activation. Our results thus implicate that epigenetic modulation of miR-124 could be considered as a potential therapeutic approach to ameliorate microglial activation and, possibly, the development of cocaine addiction.

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“…Also although miR-124 inhibited AR expression, miR-124 was positively regulated by AR, suggesting a negative feedback loop between the AR and miR-124, controlling the progression of CRPC (Shi et al 2013, Chu et al 2015. miRNAs associated with cell cycle and apoptosis in PCa miRNAs play a critical role in PCa through modulation of protein expression involved in cell cycle regulation and apoptosis, such as p53, Bcl2/Bcl-xl, E2F, cyclins, CDKs, among others (see box 3 for related terminology, Fig.…”

Section: Mir-124mentioning

confidence: 99%

Implications of microRNA dysregulation in the development of prostate cancer

et al. 2017

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MicroRNAs (miRNAs) are non-coding small RNAs that target mRNA to reduce protein expression. They play fundamental roles in several diseases, including prostate cancer (PCa). A single miRNA can target hundreds of mRNAs and coordinately regulate them, which implicates them in nearly every biological pathway. Hence, miRNAs modulate proliferation, cell cycle, apoptosis, adhesion, migration, invasion and metastasis, most of them constituting crucial hallmarks of cancer. Due to these properties, miRNAs emerged as promising tools for diagnostic, prognosis and management of cancer patients. Moreover, they come out as potential targets for cancer treatment, and several efforts are being made to progress in the field of miRNA-based cancer therapy. In this review, we will summarize the recent information about miRNAs in PCa. We will recapitulate all the miRNAs involved in the androgen pathway and the biology of PCa, focusing in PCa initiation and progression. In particular, we will describe the miRNAs associated with cell proliferation, cell cycle and apoptosis in PCa, as well as invasion, adhesion and metastatic miRNAs. We will revise the recent progress made understanding the role of circulating miRNAs identified in PCa that might be useful for PCa patient stratification. Another key aspect to be discussed in this review is miRNAs' role in PCa therapy, including the miRNAs delivery.Reproduction (2017) 154 R81-R97

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Regulation and Methylation of Tumor Suppressor MiR-124 by Androgen Receptor in Prostate Cancer Cells

Cited by 24 publications

References 28 publications

MicroRNA-124a inhibits cell proliferation and migration in liver cancer by regulating interleukin-11

MicroRNA-124a inhibits cell proliferation and migration in liver cancer by regulating interleukin-11

Cocaine-mediated downregulation of microglial miR-124 expression involves promoter DNA methylation

Implications of microRNA dysregulation in the development of prostate cancer

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