Increased microRNA-221/222 and decreased estrogen receptor α in the cervical portion of the uterosacral ligaments from women with pelvic organ prolapse

Shi, Zhonghua; Zhang, Ting; Zhang, Lei; Zhao, Jing; Gong, Jian; Zhao, Chun

doi:10.1007/s00192-012-1703-5

Cited by 11 publications

(5 citation statements)

References 24 publications

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“…While this work was in progress, Shi et al . also found that miR-222 expression is increased in the USLs of women with POP compared to normal counterparts and that there is an inverse correlation between ERα protein and miR-222 expression 33 . In conclusion, based on Shi et al .…”

Section: Discussionmentioning

confidence: 78%

MicroRNA‐30d and microRNA‐181a regulate HOXA11 expression in the uterosacral ligaments and are overexpressed in pelvic organ prolapse

Jeon

Kim

Lee

et al. 2015

J Cellular Molecular Medi

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The balanced turnover of collagen is necessary to maintain the mechanical strength of pelvic supportive connective tissues. Homeobox (HOX) A11 is a key transcriptional factor that controls collagen metabolism and homoeostasis in the uterosacral ligaments (USLs), and the deficient HOXA11 signalling may contribute to alterations in the biochemical strength of the USLs, leading to pelvic organ prolapse (POP). However, it is unknown how HOXA11 transcripts are regulated in the USLs. In this study, we found that microRNA (miRNA)-30d and 181a were overexpressed in women with POP, and their expression was inversely correlated with HOXA11 mRNA levels. The overexpression of miR-30d or 181a suppressed HOXA11 mRNA and protein levels in 293T cells, whereas the knockdown of these miRNAs enhanced HOXA11 levels and collagen production. Cotransfection of a luciferase reporter plasmid containing the 3′-untranslated region of HOXA11 with miR-30d or 181a mimic resulted in decreased relative luciferase activity. Conversely, cotransfection with anti-miR-30d or 181a increased luciferase activity. Taken together, these results indicate that both miR-30d and 181a are important posttranscriptional regulators of HOXA11 in the USLs and could be a potential therapeutic target for POP.

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Section: Discussionmentioning

confidence: 78%

MicroRNA‐30d and microRNA‐181a regulate HOXA11 expression in the uterosacral ligaments and are overexpressed in pelvic organ prolapse

Jeon

Kim

Lee

et al. 2015

J Cellular Molecular Medi

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“…reported (49). A previous study indicated that miR-221 and miR-222, two regulatory factors of ESR1, negatively regulate the expression of ESR1 in patients with POP (50). The aforementioned results demonstrated that the ESR1 genotype may be a predisposing factor for POP and that it may be used as a potential therapeutic target for this disease.…”

Section: Genetic Susceptibility and Popmentioning

confidence: 77%

Advances in molecular mechanisms of pelvic organ prolapse (Review)

et al. 2021

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Pelvic organ prolapse (POP) is a common gynecological benign disease occurring in middle-aged and elderly females. Its incidence increases every year. To date, the majority of studies investigating its etiology have not evaluated the underlying molecular mechanisms, which has caused substantial difficulties in the prevention, treatment and prognosis of POP. In the present narrative review, recent research studies concerning the molecular mechanisms of POP were systematically reviewed and the advances were summarized. The association between the incidence of POP and the reduction of the extracellular matrix, activation of oxidative stress, genetic susceptibility, denervation of the pelvic floor and reduction of estrogen infiltration were explored. POP is mainly associated with damage of pelvic floor muscles and connective tissue, which are directly caused by pregnancy and vaginal delivery. The majority of the molecular and genetic mutations associated with POP involve specific components of connective tissue synthesis and degradation. It is likely that macroscopic parameters, such as anatomy, lifestyle and reproductive factors, interact with microscopic parameters, such as physiology and genetics in the female pelvic floor, leading to POP. Additional research studies investigating the molecular mechanisms of POP should be performed, since they may aid public health strategies. In the present narrative review, a summary of these molecular mechanisms underlying the development of POP is provided. This included the relevant proteins and genes involved. On this basis, countermeasures were proposed. Contents

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“…In the miRNA–hub gene network, 96 miRNAs were found to be associated with hub genes. Previous basic research has confirmed that among these miRNAs, miRNA-19, miRNA-30, miRNA-181, miRNA-138, and miRNA-221/222 could regulate the expression of critical genes supporting the pelvic floor, such as IGF-1, HOXA11, FBLN5, and estrogen receptor [ [54] , [55] , [56] , [57] ]. In the TF–hub gene network, TFs of CREM, GTF2A2, SUZ12, ZNF2, and ZNF512 in the network exhibited a high degree of interaction.…”

Section: Discussionmentioning

confidence: 99%

Identification of potential molecular mechanisms and therapeutic targets for recurrent pelvic organ prolapse

Zhou,

Lu,

et al. 2023

Heliyon

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Increased microRNA-221/222 and decreased estrogen receptor α in the cervical portion of the uterosacral ligaments from women with pelvic organ prolapse

Abstract: Elevated miR-221/222 expression levels are associated with, and may be responsible for, reduced ERα expression in the cervical portion of uterosacral ligaments of patients with POP. MiR-221/222 may serve as potential therapeutic targets for POP.

Cited by 11 publications

References 24 publications

MicroRNA‐30d and microRNA‐181a regulate HOXA11 expression in the uterosacral ligaments and are overexpressed in pelvic organ prolapse

MicroRNA‐30d and microRNA‐181a regulate HOXA11 expression in the uterosacral ligaments and are overexpressed in pelvic organ prolapse

Advances in molecular mechanisms of pelvic organ prolapse (Review)

Identification of potential molecular mechanisms and therapeutic targets for recurrent pelvic organ prolapse

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