m6A RNA Methylation Regulators Contribute to Eutopic Endometrium and Myometrium Dysfunction in Adenomyosis

Zhai, Junyu; Li, Shang; Sen, Sushmita; Opoku‐Anane, Jessica; Du, Yanzhi; Chen, Zi‐Jiang; Giudice, Linda C.

doi:10.3389/fgene.2020.00716

Cited by 28 publications

(26 citation statements)

References 61 publications

(74 reference statements)

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“…Thus, m 6 A RNA methylation regulators may be involved in the pathogenesis of adenomyosis through aberrant expression and actions in both the uterine endometrium and myometrium. 96…”

Section: Epigeneticsmentioning

confidence: 99%

Adenomyosis: Mechanisms and Pathogenesis

et al. 2020

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Adenomyosis is a common disorder of the uterus, and is associated with an enlarged uterus, heavy menstrual bleeding (HMB), pelvic pain, and infertility. It is characterized by endometrial epithelial cells and stromal fibroblasts abnormally found in the myometrium where they elicit hyperplasia and hypertrophy of surrounding smooth muscle cells. While both the mechanistic processes and the pathogenesis of adenomyosis are uncertain, several theories have been put forward addressing how this disease develops. These include intrinsic or induced (1) microtrauma of the endometrial–myometrial interface; (2) enhanced invasion of endometrium into myometrium; (3) metaplasia of stem cells in myometrium; (4) infiltration of endometrial cells in retrograde menstrual effluent into the uterine wall from the serosal side; (5) induction of adenomyotic lesions by aberrant local steroid and pituitary hormones; and (6) abnormal uterine development in response to genetic and epigenetic modifications. Dysmenorrhea, HMB, and infertility are likely results of inflammation, neurogenesis, angiogenesis, and contractile abnormalities in the endometrial and myometrial components. Elucidating mechanisms underlying the pathogenesis of adenomyosis raise possibilities to develop targeted therapies to ameliorate symptoms beyond the current agents that are largely ineffective. Herein, we address these possible etiologies and data that support underlying mechanisms.

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“…Thus, m 6 A RNA methylation regulators may be involved in the pathogenesis of adenomyosis through aberrant expression and actions in both the uterine endometrium and myometrium. 96…”

Section: Epigeneticsmentioning

confidence: 99%

Adenomyosis: Mechanisms and Pathogenesis

et al. 2020

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“…In addition, PLAC8 is identified in placental functions, and PLAC8 is relatively higher in placentitis cells [103]. PLAC8 mRNA is also increased in the myometrium of adenomyosis patients, indicating the role of the immune response in the myometrium of women with adenomyosis [104]. These evidences suggest that PLAC8 may play an important role in immune system [31,105,106].…”

Section: Cancer Immunitymentioning

confidence: 85%

“…There is mounting evidence of the potential role of PLAC8-regulated network in cancer (Fig. 4) [104,111,112]. PLAC8 can be regulated at the transcriptional level.…”

Section: Overview Of the Plac8-regulated Networkmentioning

confidence: 99%

Multifaced roles of PLAC8 in cancer

et al. 2021

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The role of PLAC8 in tumorigenesis has been gradually elucidated with the development of research. Although there are common molecular mechanisms that enforce cell growth, the impact of PLAC8 is varied and can, in some instances, have opposite effects on tumorigenesis. To systematically understand the role of PLAC8 in tumors, the molecular functions of PLAC8 in cancer will be discussed by focusing on how PLAC8 impacts tumorigenesis when it arises within tumor cells and how these roles can change in different stages of cancer progression with the ultimate goal of suppressing PLAC8-relevant cancer behavior and related pathologies. In addition, we highlight the diversity of PLAC8 in different tumors and its functional output beyond cancer cell growth. The comprehension of PLAC8’s molecular function might provide new target and lead to the development of novel anticancer therapies.

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“…MiRNAs are short (20–22 nt) and highly stable RNAs that are involved in post‐transcriptional regulation of gene expression 18 . It was reported that m 6 A RNA methylation regulators contribute to eutopic endometrium and myometrium dysfunction in adenomyosis 19 . It is known that miRNA‐2861 can suppress proliferation and induce apoptosis of ectopic endometrial cells by targeting STAT3 and MMP2 20 .…”

Section: Introductionmentioning

confidence: 99%

“…18 It was reported that m 6 A RNA methylation regulators contribute to eutopic endometrium and myometrium dysfunction in adenomyosis. 19 It is known that miRNA-2861 can suppress proliferation and induce apoptosis of ectopic endometrial cells by targeting STAT3 and MMP2. 20 LncRNAs have been demonstrated to regulate gene expression through sponging miRNAs or competing endogenous RNA (ceRNA).…”

Section: Introductionmentioning

confidence: 99%

LncRNA MIR22HG is downregulated in adenomyosis and upregulates miR‐2861 through demethylation to inhibit endometrial cell proliferation

Cui

Xue

2021

J of Obstet and Gynaecol

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Aim Endometrial cell proliferation plays a critical role in adenomyosis. It has been reported that MIR22HG and miR‐2861 play similar roles in regulating endometrial cell proliferation, indicating their involvement in adenomyosis. This study aimed to investigate the potential involvement of MIR22HG and miR‐2861 in adenomyosis. Methods Endometrial biopsy was collected from both adenomyosis (n = 45) and the healthy controls (n = 45). The expression of MIR22HG and miR‐2861 in biopsies were determined by quantitative reverse transcription polymerase chain reaction (RT‐qPCR). The relationship between MIR22HG and miR‐2861 in endometrial cells was analyzed by RT‐qPCR. Methylation‐specific PCR (MSP) was performed to analyze the effects of overexpression of MIR22HG on the expression of miR‐2861. Western‐blot assays were performed to illustrate the effect of MIR22HG, miR‐2861, STAT3, and MMP2 on adenomyosis. Luciferase report assay was performed to analyze the interactions among miR‐2861, STAT3, and MMP2. The role of MIR22HG and miR‐2861 in regulating the proliferation of endometrial cells was analyzed by cell proliferation assay. Results The expression of MIR22HG and miR‐2861 in adenomyosis did not change with menstrual cycle. MIR22HG and miR‐2861 were significantly downregulated in adenomyosis and they were significantly and positively correlated with each other. In endometrial cells, overexpression of MIR22HG upregulated the expression of miR‐2861 and decreased methylation of miR‐2861 gene. MIR22HG and miR‐2861 downregulated STAT3 and MMP2 to inhibit the proliferation of endometrial cells. In addition, overexpression of both MIR22HG and miR‐2861 showed stronger effects. Conclusion MIR22HG is downregulated in adenomyosis and upregulates miR‐2861 through demethylation to inhibit endometrial cell proliferation.

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m6A RNA Methylation Regulators Contribute to Eutopic Endometrium and Myometrium Dysfunction in Adenomyosis

Cited by 28 publications

References 61 publications

Adenomyosis: Mechanisms and Pathogenesis

Adenomyosis: Mechanisms and Pathogenesis

Multifaced roles of PLAC8 in cancer

LncRNA MIR22HG is downregulated in adenomyosis and upregulates miR‐2861 through demethylation to inhibit endometrial cell proliferation

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