Next-generation sequencing reveals differentially expressed small noncoding RNAs in uterine leiomyoma

Chuang, Tsai‐Der; Xie, Yeming; Yan, Wei; Khorram, Omid

doi:10.1016/j.fertnstert.2018.01.034

Cited by 23 publications

(16 citation statements)

References 68 publications

(73 reference statements)

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“…Immunoblotting. Immunoblotting was performed following previously described methods (15,18). Briefly, samples were suspended in RIPA buffer containing 1 mM EDTA and EGTA (Boston BioProducts, Ashland, MA) supplemented with 1 mM PMSF and a complete protease inhibitor mixture (Roche Diagnostics, Indianapolis, IN), sonicated, and centrifuged at 4°C for 10 min at 14,000 rpm.…”

Section: Methodsmentioning

confidence: 99%

Mechanism underlying increased cardiac extracellular matrix deposition in perinatal nicotine-exposed offspring

Chuang

Ansari

et al. 2020

American Journal of Physiology-Heart and Circulatory Physiology

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Although increased predisposition to cardiac fibrosis and cardiac dysfunction has been demonstrated in the perinatally nicotine exposed heart, the underlying mechanisms remain unclear. Using a well-established rat model and cultured primary neonatal rat cardiac fibroblasts, the effect of perinatal nicotine exposure on offspring heart extracellular matrix deposition and the likely underlying mechanisms were investigated. Perinatal nicotine exposure resulted in increased collagen type I (COL1A1) and III (COL3A1) deposition along with a decrease in miR-29 family and an increase in long non-coding RNA myocardial infarction associated transcript (MIAT) levels in offspring heart. Nicotine treatment of isolated primary neonatal rat cardiac fibroblasts suggested that these effects were mediated via nicotinic acetylcholine receptors including α7 and the induced collagens accumulation was reversed by a gain-of function of miR-29 family. Knockdown of MIAT resulted in increased miR-29 family and decreased COL1A1 and COL3A1 levels, suggesting nicotine-mediated MIAT induction as the underlying mechanism for nicotine-induced collagen deposition. Luciferase reporter assay and RNA immunoprecipitation studies showed an intense physical interaction between MIAT, miR-29 family, and argonaute 2, corroborating the mechanistic link between perinatal nicotine exposure and increased extracellular matrix deposition. Overall, perinatal nicotine exposure resulted in lower miR-29 family levels in offspring heart, while it elevated cardiac MIAT and collagen type I and III levels. These findings provide mechanistic basis for cardiac dysfunction in perinatal nicotine exposed offspring and offer multiple novel potential therapeutic targets.

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Section: Methodsmentioning

confidence: 99%

Mechanism underlying increased cardiac extracellular matrix deposition in perinatal nicotine-exposed offspring

Chuang

Ansari

et al. 2020

American Journal of Physiology-Heart and Circulatory Physiology

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“…Total protein isolated from LSMC following treatment conditions was subjected to immunoblotting as previously described (12,37). Briefly, samples were suspended in RIPA buffer containing 1 mmol/L EDTA and EGTA (Boston Bioproducts) supplemented with 1 mmol/L PMSF and a complete protease inhibitor mixture (Roche Diagnostics), sonicated, and centrifuged at 4 C for 10 minutes at 14,000 rpm.…”

Section: Immunoblottingmentioning

confidence: 99%

“…Accumulated proteomic and genomic studies have indicated that altered expression of small noncoding RNAs, including microRNAs (miRNAs), play a key role in cellular events leading to leiomyoma development and growth (5,(8)(9)(10)(11)(12). More specifically, our laboratory and others have provided evidence that the expression of the miR-200 and miR-29 family are suppressed in leiomyoma and that their altered expression accounts at least in part for the molecular mechanism underlying ECM accumulation, angiogenesis, and inflammation (13)(14)(15)(16)(17).…”

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confidence: 96%

Tranilast induces MiR-200c expression through blockade of RelA/p65 activity in leiomyoma smooth muscle cells

Chuang

Rehan

Khorram

2020

Fertility and Sterility

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Objective: To determine the mechanism by which tranilast induces miR-200c expression in leiomyoma smooth muscle cells (LSMCs). Design: Experimental study. Setting: Academic research laboratory. Patient(s): Women undergoing hysterectomy for leiomyoma. Intervention(s): Blockade of RelA/p65. Main Outcome Measure(s): Effects of tranilast and blockade of RelA/p65 on miR-200c expression. Result(s): Tranilast, an inflammation inhibitor, dose-dependently induced miR-200c in LSMCs and myometrium smooth muscle cells (MSMCs), with a more profound effect in LSMCs than in MSMCs. The treatment of LSMCs with Bay 117082, an inhibitor of IkB phosphorylation, further enhanced miR-200c induction by tranilast. The knockdown of RelA/p65 by small interfering RNA also induced miR-200c expression in LSMCs. Although tranilast had no effect on total RelA/p65 protein levels in LSMCs, it significantly induced RelA/p65 phosphorylation at S536 while reducing its activity as well as its nuclear translocation. ChIP assay indicated that tranilast reduces the binding ability of RelA/p65 to miR-200c promoter, resulting in miR-200c induction. Tranilast also inhibited interleukin-8 (IL8) expression in LSMCs. The induction of miR-200c by tranilast partially mediates the inhibitory effect of tranilast on the expression of IL8 and cyclin-dependent kinase 2 in LSMCs. Conclusion(s): Induction of miR-200c by tranilast in LSMCs is mediated through a transcriptional mechanism involving inhibition of the nuclear factor kB signaling pathway. These results highlight the significance of inflammation in the pathogenesis of leiomyoma and the potential utility of antiinflammatory drugs for treatment of leiomyomas. (Fertil Steril Ò 2020;113:1308-18. Ó2019 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.

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“…Uterine leiomyoma (UL) are the common benign neoplastic disease among women worldwide. Screening the RNA-sequencing data with the sncRNA database leaded to the findings that 24 piRNAs were differentially expressed by more than 1.5 fold in UL compared to adjacent normal myometrium [89]. For future study, it would be interesting to determine their molecular functions in the UL.…”

Section: Pirnas In Other Types Of Diseasesmentioning

confidence: 99%

The disease-related biological functions of PIWI-interacting RNAs (piRNAs) and underlying molecular mechanisms

Han

2019

ExRNA

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More than a decade ago, PIWI-interacting RNA (piRNA) was discovered almost simultaneously by four different research groups. The length of this type of single stranded noncoding RNA is 24~31 nucleotides (nt), with most of the piRNAs fall into the range of 29~30 nt. PiRNAs form specific RNA-induced silencing complex with PIWI subfamily proteins, which is how piRNA got its name. PiRNAs are initially famous for the crucial roles they played in germline cells. Binding with PIWI family proteins, piRNAs is able to affect methylation of genomic DNA in germline cells and, therefore, maintaining genomic stability and suppressing transposons. Since mammalian PIWI subfamily proteins are mainly germline specific, it was once thought that piRNAs might only function in the gonadal cells. However, evidence from the later research suggest that piRNAs are broadly expressed in many kinds of somatic cells and are involved in numerous pathological condition far beyond those have been reported in the germline. For example, piRNAs were discovered to be abnormally expressed in several kinds of cancers. PiRNAs are also shown to be promising prognostic markers for various types of cancers. Interestingly, a recent research indicated that piRNAs are also regulators for pancreatic beta cell function. PiRNAs are promising regulators for the development of type 2 diabetes. From a disease-oriented point of view, this review will focus on both confirmed and proposed biological functions of piRNAs mostly in those fields beyond germline cells. Meanwhile, some of the underlying molecular mechanisms will also be mentioned.

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Next-generation sequencing reveals differentially expressed small noncoding RNAs in uterine leiomyoma

Abstract: Our results provide the first evidence for the differential expression of additional classes of sncRNAs and AGO2 in leiomyoma, implicating their roles as a gene regulatory mechanism.

Cited by 23 publications

References 68 publications

Mechanism underlying increased cardiac extracellular matrix deposition in perinatal nicotine-exposed offspring

Mechanism underlying increased cardiac extracellular matrix deposition in perinatal nicotine-exposed offspring

Tranilast induces MiR-200c expression through blockade of RelA/p65 activity in leiomyoma smooth muscle cells

The disease-related biological functions of PIWI-interacting RNAs (piRNAs) and underlying molecular mechanisms

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