title: MicroRNA-30d and microRNA-181a regulate HOXA11 expression in the uterosacral ligaments and are overexpressed in pelvic organ prolapse.
abstract: 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.
authors: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
authors: Myung Jae
authors: MJ
authors: Jeon
authors: Eun Jae
authors: EJ
authors: Kim
authors: Maria
authors: M
authors: Lee
authors: Hoguen
authors: H
authors: Kim
authors: Jong Rak
authors: JR
authors: Choi
authors: Hee Dong
authors: HD
authors: Chae
authors: Yeo Jung
authors: YJ
authors: Moon
authors: Sei Kwang
authors: SK
authors: Kim
authors: Sang Wook
authors: SW
authors: Bai
mesh_terms: D002460:Cell Line; D003238:Connective Tissue / Q000378:metabolism; D005260:Female; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008022:Ligaments / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D056887:Pelvic Organ Prolapse / Q000378:metabolism*; D014599:Uterus / Q000378:metabolism*
chemical_list: C484298:HOXA11 protein, human; D018398:Homeodomain Proteins; C546086:MIRN30b microRNA, human; C540193:MIrn181 microRNA, human; D035683:MicroRNAs
keywords: HOXA11; microRNA; pelvic organ prolapse; uterosacral ligament
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