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

Authors
 Myung Jae Jeon  ;  Eun Jae Kim  ;  Maria Lee  ;  Hoguen Kim  ;  Jong Rak Choi  ;  Hee Dong Chae  ;  Yeo Jung Moon  ;  Sei Kwang Kim  ;  Sang Wook Bai 
Citation
 JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Vol.19(2) : 501-509, 2015 
Journal Title
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
ISSN
 1582-1838 
Issue Date
2015
MeSH
Cell Line ; Connective Tissue/metabolism ; Female ; HEK293 Cells ; Homeodomain Proteins/metabolism* ; Humans ; Ligaments/metabolism* ; MicroRNAs/metabolism* ; Middle Aged ; Pelvic Organ Prolapse/metabolism* ; Uterus/metabolism*
Keywords
HOXA11 ; microRNA ; pelvic organ prolapse ; uterosacral ligament
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.
Files in This Item:
T201500382.pdf Download
DOI
10.1111/jcmm.12448
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sei Kwang(김세광)
Kim, Hogeun(김호근)
Moon, Yeo Jung(문여정)
Bai, Sang Wook(배상욱) ORCID logo https://orcid.org/0000-0001-7724-7552
Choi, Jong Rak(최종락) ORCID logo https://orcid.org/0000-0002-0608-2989
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/139451
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