Differential expression of estrogen receptor α and β isoforms in multiple and solitary leiomyomas

Shao, Ruyue; Fang, Liaoqiong; Xing, Ruoxi; Xiong, Yan‐Li; Wang, Zhibiao

doi:10.1016/j.bbrc.2015.10.145

Cited by 14 publications

(8 citation statements)

References 29 publications

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“…Mutation of MED12 and rearrangement of HMGA2 are the most common genetic subtypes in UL according to a recent study [23]. Moreover, the mutation of MED12 was shown to be more common in MUL patients, while the mutation of HMGA2 was largely observed in SUL cases, and no single patient exhibited both mutations simultaneously [24, 25]. As UL is a sex hormone-induced tumor, the difference between SUL and MUL also involves the expression of estrogen receptor (ER), with lower expression of ERα and higher expression of ERβ in MUL than in SUL [26].…”

Section: Discussionmentioning

confidence: 99%

Lnc-AL445665.1–4 may be involved in the development of multiple uterine leiomyoma through interacting with miR-146b-5p

Yang

et al. 2019

BMC Cancer

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Background The clinical behaviors and cytogenetics of solitary uterine leiomyomas (SUL) and multiple uterine leiomyomas (MUL) vary, which greatly affects the choice of treatments for reproductive-aged patients with leiomyomas. Our previous study demonstrated that a series of microRNAs, including miR-146b-5p, are dysregulated and play important roles in the development of SUL and MUL. Long non-coding RNAs (lncRNAs) can participate in the pathogenesis of several diseases by regulating the expression of microRNAs; however, their roles in regulating miR-146b-5b and in the pathology of leiomyomas are unclear. Methods Pair-matched uterine leiomyoma and adjacent normal myometrium tissue samples were collected from 37 patients with leiomyomas, including 15 with SUL and 22 with MUL. Six paired samples (three SUL and three MUL samples) were used for lncRNAs microarray analysis. Targeted lncRNAs were selected by bioinformatics analysis, and were verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and a dual-luciferase reporter assay. Growth curve analysis and qRT-PCR were used to evaluate the effect of silencing the lncRNA lnc-AL445665.1–4 on cell proliferation and miR-146b-5p expression, respectively. Results There were 245 up-regulated and 243 down-regulated lncRNAs in SUL, and 119 up-regulated and 447 down-regulated lncRNAs in MUL. Fifty-five of the selected lncRNAs were predicted to target miR-146b-5p, which is up-regulated in SUL and down-regulated in MUL. Four lncRNAs were selected after Venn diagram analysis showing common dysregulation in the three groups. Lnc-AL445665.1–4 was selected for further exploration. qRT-PCR showed that lnc-AL445665.1–4 expression was significantly up-regulated in MUL compared with SUL in an additional 12 and 19 paired SUL-normal and MUL-normal samples, respectively. The dual-luciferase reporter assay demonstrated the presence of binding sites on lnc-AL445665.1 for miR-146b-5p. Silencing lnc-AL445665.1–4 not only inhibited cell proliferation but also negatively regulated the expression of miR-146b-5p. Conclusions Our results suggest that lnc-AL445665.1–4 may be involved in the development of MUL by interacting with miR-146b-5p. Further investigation of the roles of lncRNAs and miRNAs may help to optimize the clinical management of leiomyoma patients. Lnc-AL445665.1–4 could be a novel target for genetic therapy or serve as a biomarker for predicting the recurrence of MUL in patients that have undergone myomectomy. Electronic supplementary material The online version of this article (10.1186/s12885-019-5775-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Lnc-AL445665.1–4 may be involved in the development of multiple uterine leiomyoma through interacting with miR-146b-5p

Yang

et al. 2019

BMC Cancer

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“…In The Ontario Uterine Fibroid Embolization Trial, the majority of women undergoing uterine artery embolisation had multiple fibroids with this tendency being more strongly pronounced in black compared with white women 25. Solitary and multiple fibroids show differential expression of oestrogen receptor α and β isoforms 26. In contrast to women with solitary ULs, women with multiple ULs have lower prevalence of protective CYP17A1 AA genotype (–34 A→G, rs743572) and lower CYP17A1 A allele frequency than healthy controls 27.…”

Section: Discussionmentioning

confidence: 99%

Catechol-O-methyltransferase Val158Met polymorphism is associated with increased risk of multiple uterine leiomyomas either positive or negative forMED12exon 2 mutations

et al. 2016

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“…Shao et al . [18] demonstrated that 17ß-estradiol concentrations were lower in multiple ULM compared to solitary ULM.…”

Section: Discussionmentioning

confidence: 99%

“…Some of these studies reported a significant association between IL4, IL1B and IL12RB1 and ULM development [13-15]. In addition, clinical and genetic differences have been noted between subtypes of solitary and multiple ULM [17, 18]. In this study, however, we focused on cytokines derived from τ helper type 2 (Th2) cells (IL-4, IL-12 and IL-13), hypothesizing that they might be good candidates as they are involved in the avoidance of tumor immuno-surveillance at the molecular level.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, some functional studies showed effect of SNPs in IL4 and IL4R genes on their expression, particularly SNP in the IL4 gene correlates with enhanced IL-4 activity [20] and SNP in the IL4R gene functionally impacts the signaling and upregulating of the receptor’s response to IL-4, which in turn results in activation of the STAT6 pathway [21]. Recently, clinical and genetic differences were noted between subtypes of solitary and multiple ULM [17, 18]. The aim of our study was to further evaluate polymorphisms in genes coding for ILs, specifically SNPs with a known functional role in IL expression, including IL4 and IL4R , SNPs with previously contradictory results in different populations, including IL12RB1 , as well as SNPs previously not yet analyzed for ULM, including IL12B, IL23R and IL13 .…”

Section: Introductionmentioning

confidence: 99%

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Polymorphism of theIL13gene may be associated with Uterine leiomyomas in Slovenian women

Krsteski

Jurgec

Pakiž

et al. 2016

Balkan Journal of Medical Genetics

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Uterine leiomyomas (ULM) are a common cause of solid pelvic tumors in women. Their etiopathogenesis remains unclear. Interleukins (ILs) and their receptors can influence tumor biology of ULM. The aim of this study was to evaluate single nucleotide polymorphisms (SNPs) exhibited in the genes IL4 (rs2070874), IL4R (rs1801275), IL12RB1 (rs11575934), IL12B (rs6887695), IL13 (rs20541) and IL23R (rs7517847) as risk factors for ULM in Slovenian women and to identify associations between corresponding clinical parameters and the analyzed SNPs. In addition, solitary and multiple ULM were compared to identify clinical and/or genetic parameters influencing their occurrence. We conducted a case-control study that included 181 women with leiomyomas and 133 control subjects. Genotyping of selected SNPs was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and high resolution melting (HRM) techniques. The TT genotype of rs20541 (IL13) was significantly associated with decreased risk of ULM compared to both the CC and CT genotypes [p = 0.018; odds ratio (OR) = 0.184; 95% confidence interval (95% CI) = 0.048-0.7121. Using genetic and clinical data to develop a predictive model with logistic regression, we found that adenomyosis, higher age at diagnosis, family history of ULM occurrence, earlier menarche, lower number of pregnancies and lower age at first sexual intercourse, the G allele and genotypes AG and GG of rs1801275 (IL4R) were associated with an increased risk of multiple ULM occurrence. We also found an association between rs20541 (IL13) and 17ß-estradiol serum levels in patients with multiple ULM (p 0.003). Our study showed, for the first time, that rs20541 (IL13) may contribute to susceptibility of ULM development and that rs1801275 (IL4R) can predispose patients to develop multiple ULM.

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Differential expression of estrogen receptor α and β isoforms in multiple and solitary leiomyomas

Cited by 14 publications

References 29 publications

Lnc-AL445665.1–4 may be involved in the development of multiple uterine leiomyoma through interacting with miR-146b-5p

Lnc-AL445665.1–4 may be involved in the development of multiple uterine leiomyoma through interacting with miR-146b-5p

Catechol-O-methyltransferase Val158Met polymorphism is associated with increased risk of multiple uterine leiomyomas either positive or negative forMED12exon 2 mutations

Polymorphism of theIL13gene may be associated with Uterine leiomyomas in Slovenian women

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