Coordination of AUF1 and miR-148a destabilizes DNA methyltransferase 1 mRNA under hypoxia in endometriosis

Hsiao, Kuei‐Yang; Wu, Meng Hsing; Chang, Ning; Yang, Shang Hsun; Wu, Chi Jung; Sun, Hui-Lung; Tsai, Shaw-Jenq

doi:10.1093/molehr/gav054

Cited by 50 publications

(46 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…37, 38, 39 In a previous study, DNMT1 could hypermethylate the miR-148a gene promoters in breast cancer tissues, and DNMT1 overexpression resulted in miR-148a hypermethylation. 27 In our study, we found that miR-148a-3p surrounding CpG islands were hypermethylated in bladder cancer and that treatment with 5-aza-CdR induced miR-148a-3p overexpression in bladder cancer.…”

Section: Discussionmentioning

confidence: 93%

miR-148a-3p represses proliferation and EMT by establishing regulatory circuits between ERBB3/AKT2/c-myc and DNMT1 in bladder cancer

Wang

Liang

et al. 2016

Cell Death Dis

View full text Add to dashboard Cite

miR-148a-3p downregulation has emerged as a critical factor in cancer progression yet, the underlying mechanisms of miR-148a-3p expression pattern and its function in bladder cancer remains to be elucidated. Here, we illustrate that miR-148a-3p is frequently downregulated in bladder cancer and that its expression may be regulated by DNA methylation. DNA methyltransferase 1 (DNMT1) and miR-148a-3p function in a positive feedback loop in bladder cancer. miR-148a-3p overexpression functions as a tumor suppressor in bladder cancer cells. miR-148a-3p inhibits bladder cancer cell proliferation and epithelial–mesenchymal transition (EMT) by regulating ERBB3/AKT2/c-myc and ERBB3/AKT2/Snail signaling. ERBB3, DNMT1 and AKT2 are downstream miR-148a-3p target genes. Furthermore, the miR-148a-3p/ERBB3/AKT2/c-myc signaling axis establishes a positive feedback loop in the regulation of bladder cancer. Taken together, our study demonstrates novel regulatory circuits involving miR-148a-3p/ERBB3/AKT2/c-myc and DNMT1 that controls bladder cancer progression, which may be useful in the development of more effective therapies against bladder cancer.

show abstract

Section: Discussionmentioning

confidence: 93%

miR-148a-3p represses proliferation and EMT by establishing regulatory circuits between ERBB3/AKT2/c-myc and DNMT1 in bladder cancer

Wang

Liang

et al. 2016

Cell Death Dis

View full text Add to dashboard Cite

show abstract

“…Our group has also shown relevance of RNABPs including TTP and HuR as well as localization of TTP in inflammatory conditions using a mouse model of recurrent pregnancy loss 25 . Other RNA binding proteins such as AUF1 have also been shown to have indirect effects by influencing methylation under hypoxic conditions in endometriosis 26 . The adult stem cell marker RNA binding protein, Musashi-1 has been shown to be increased in endometriosis and endometrial carcinomas 27 .…”

Section: Introductionmentioning

confidence: 99%

A balancing act: RNA binding protein HuR/TTP axis in endometriosis patients

Khalaj

Ahn

Bidarimath

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Endometriosis, a major reproductive pathology affecting 8–10% of women is characterized by chronic inflammation and immune dysfunction. Human antigen R (HuR) and Tristetraprolin (TTP) are RNA binding proteins that competitively bind to cytokines involved in inflammation including: tumor necrosis factor alpha (TNF-α), granulocyte macrophage colony stimulating factor (GM-CSF), interleukin 6 (IL-6) among others, and stabilize and destabilize them, respectively. The aim of this study was to examine RNA binding protein (RNABP) HuR/TTP axis in endometriosis patients compared to menstrual stage matched healthy fertile controls in hopes of better understanding their contribution to the pathogenesis of endometriosis. Additionally, using a targeted in vitro siRNA approach, we examined whether knock-down of TTP can play a functional role on other RNABPs that competitively bind to inflammatory targets of TTP in both endometriotic and endometrial epithelial cell lines. Our results suggest that RNABPs TTP and HuR are dysregulated in endometriotic lesions compared to matched eutopic patient samples as well endometrium from healthy controls. Silencing of TTP in endometriotic and endometrial epithelial cells revealed differential response to inflammatory cytokines and other RNABPs. Our results suggest potential involvement of HuR/TTP RNA binding protein axis in regulation of inflammation in endometriosis.

show abstract

“…These studies indicate that hypoxia promotes the development of endometriosis through various mechanisms. More importantly, a recent study demonstrates that hypoxia causes epigenome reprogramming by stimulating the degradation of DNA methyltransferase 1 mRNA, which results in altering the expression profile of some critical genes involved in the development/progression of endometriosis (Hsiao et al 2015). This suggests that hypoxia may contribute to endometriosis by means of another layer of gene regulation.…”

Section: Endometriosismentioning

confidence: 99%

Endocrine targets of hypoxia-inducible factors

Lee

Tsai

2017

Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

Endocrine is an important and tightly regulated system for maintaining body homeostasis. Endocrine glands produce hormones, which are released into blood stream to guide the target cells responding to all sorts of stimulations. For maintaining body homeostasis, the secretion and activity of a particular hormone needs to be adjusted in responding to environmental challenges such as changes in nutritional status or chronic stress. Hypoxia, a status caused by reduced oxygen availability or imbalance of oxygen consumption/supply in an organ or within a cell, is a stress that affects many physiological and pathological processes. Hypoxic stress in endocrine organs is especially critical because endocrine glands control body homeostasis. Local hypoxia affects not only the particular gland but also the downstream cells/organs regulated by hormones secreted from this gland. Hypoxia-inducible factors (HIFs) are transcription factors that function as master regulators of oxygen homeostasis. Recent studies report that aberrant expression of HIFs in endocrine organs may result in the development and/or progression of diseases including diabetes, endometriosis, infertility and cancers. In this article, we will review recent findings in HIF-mediated endocrine organ dysfunction and the systemic syndromes caused by these disorders.

show abstract

Coordination of AUF1 and miR-148a destabilizes DNA methyltransferase 1 mRNA under hypoxia in endometriosis

Abstract: This work was supported by the National Science Council of Taiwan (NSC101-2320-B-006-030-MY3). The author declares that there are no conflicts of interest.

Cited by 50 publications

References 38 publications

miR-148a-3p represses proliferation and EMT by establishing regulatory circuits between ERBB3/AKT2/c-myc and DNMT1 in bladder cancer

miR-148a-3p represses proliferation and EMT by establishing regulatory circuits between ERBB3/AKT2/c-myc and DNMT1 in bladder cancer

A balancing act: RNA binding protein HuR/TTP axis in endometriosis patients

Endocrine targets of hypoxia-inducible factors

Contact Info

Product

Resources

About