Overexpression of Igf2-derived Mir483 inhibits Igf1 expression and leads to developmental growth restriction and metabolic dysfunction in mice

被引：1

作者：

Sandovici, Ionel ^{[1
,2
,3
,4
]}

Fernandez-Twinn, Denise S. ^{[1
]}

Campbell, Niamh ^{[1
,2
,3
]}

Cooper, Wendy N. ^{[1
,2
,3
,13
]}

Sekita, Yoichi ^{[1
,2
,3
,14
]}

Zvetkova, Ilona ^{[1
]}

Ferland-McCollough, David ^{[5
,15
]}

Prosser, Haydn M. ^{[6
,16
,17
]}

Oyama, Lila M. ^{[1
,7
]}

Pantaleao, Lucas C. ^{[1
]}

Cimadomo, Danilo ^{[2
,3
,8
,18
]}

de Queiroz, Karina Barbosa ^{[2
,3
,19
]}

Cheuk, Cecilia S. K. ^{[2
,3
,9
]}

Smith, Nicola M. ^{[1
,20
]}

Kay, Richard G. ^{[1
]}

Antrobus, Robin ^{[10
,11
]}

Hoelle, Katharina ^{[2
,3
]}

Ma, Marcella K. L. ^{[1
]}

Smith, Noel H. ^{[1
,21
]}

Geyer, Stefan H. ^{[12
]}

Reissig, Lukas F. ^{[12
]}

Weninger, Wolfgang J. ^{[5
,12
]}

Siddle, Kenneth ^{[1
,6
]}

Willis, Anne E. ^{[5
,22
]}

Lam, Brian Y. H. ^{[1
,7
]}

Bushell, Martin ^{[5
,23
,24
]}

Ozanne, Susan E. ^{[1
,4
]}

Constancia, Miguel ^{[1
,2
,3
,4
]}

机构：

[1] Univ Cambridge, Inst Metab Sci, Med Res Council, Metab Res Labs,Metab Dis Unit, Cambridge, England

[2] Cambridge Biomed Res Ctr, Dept Obstet & Gynaecol, Cambridge, England

[3] Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge, England

[4] Univ Cambridge, Ctr Trophoblast Res, Dept Physiol Dev & Neurosci, Cambridge, England

[5] Univ Leicester, Med Res Council, Toxicol Unit, Leicester, England

[6] Wellcome Trust Sanger Inst, Genome Campus, Hinxton, England

[7] Univ Fed Sao Paulo, Departmento Fisiol, Escola Paulista Med, Sao Paulo, Brazil

[8] Univ Pavia, Dept Biol & Biotechnol Lazzaro Spallanzani, Lab Dev Biol, Pavia, Italy

[9] Univ Oxford, Nuffield Dept Womens & Reprod Hlth, Oxford, England

[10] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England

[11] Univ Cambridge, Dept Med, Cambridge, England

[12] Med Univ Vienna, Ctr Anat & Cell Biol, Div Anat, Vienna, Austria

[13] Canc Res UK Cambridge Ctr, Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Cambridge, England

[14] Kitasato Univ, Sch Sci, Dept Biosci, Lab Stem Cell Biol, Minato, Kanagawa, Japan

[15] Inst Rech Clin Montreal, Montreal, PQ, Canada

[16] Univ Cambridge, Cambridge Inst Therapeut Immunol & Infect Dis, Jeffrey Cheah Biomed Ctr, Cambridge, England

[17] Univ Cambridge, Jeffrey Cheah Biomed Ctr, Dept Med, Cambridge, England

[18] Genera, IVIRMA Global Res Alliance, Clin Valle Giulia, Rome, Italy

[19] Univ Fed Ouro Preto, Escola Nutr, Dept Alimentos, Programa Posgrad Saude & Nutr, Ouro Preto, Brazil

[20] Norwegian Inst Publ Hlth, Oslo, Norway

[21] Lonza Biol, Chesterford Res Pk, Saffron Walden, England

[22] Univ Cambridge, Med Res Council, Toxicol Unit, Cambridge, England

[23] Canc Res UK Beatson Inst, Glasgow, Scotland

[24] Univ Glasgow, Inst Canc Sci, Glasgow, Scotland

来源：

CELL REPORTS | 2024年 / 43卷 / 09期

基金：

英国医学研究理事会; 英国生物技术与生命科学研究理事会; 日本学术振兴会;

关键词：

GENE-EXPRESSION; INSULIN; MICRORNAS; MOUSE; MIR-483-3P; RECEPTORS; DELETION; BETA; PROLIFERATION; SUPPRESSES;

D O I：

10.1016/j.celrep.2024.114750

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Mir483 is a conserved and highly expressed microRNA in placental mammals, embedded within the Igf2 gene. Its expression is dysregulated in a number of human diseases, including metabolic disorders and certain cancers. Here, we investigate the developmental regulation and function of Mir483 in vivo. We find that Mir483 expression is dependent on Igf2 transcription and the regulation of the Igf2/H19 imprinting control region. Transgenic Mir483 overexpression in utero causes fetal, but not placental, growth restriction through insulin-like growth factor 1 (IGF1) and IGF2 and also causes cardiovascular defects leading to fetal death. Overexpression of Mir483 post-natally results in growth stunting through IGF1 repression, increased hepatic lipid production, and excessive adiposity. IGF1 infusion rescues the post-natal growth restriction. Our findings provide insights into the function of Mir483 as a growth suppressor and metabolic regulator and suggest that it evolved within the INS-IGF2-H19 transcriptional region to limit excessive tissue growth through repression of IGF signaling.

引用

页数：29

共 4 条

[1] High expression of IGF2-derived intronic miR-483 predicts outcome in hepatoblastoma
Weiss, Jakob Benjamin Wilhelm
Wagner, Alexandra Elisabeth
Eberherr, Corinna
Haeberle, Beate
Vokuhl, Christian
Schweinitz, Dietrich von
Kappler, Roland
CANCER BIOMARKERS, 2020, 28 (03) : 321 - 328
[2] IGF2-derived miR-483 mediated oncofunction by suppressing DLC-1 and associated with colorectal cancer
Cui, Hengmi
Liu, Yuan
Jiang, Jingrui
Liu, Yangyang
Yang, Zhe
Wu, Shaogen
Cao, Wangsen
Cui, Isabelle H.
Yu, Chenggong
ONCOTARGET, 2016, 7 (30): : 48456 - 48466
[3] miR-483 is Down-Regulated in Polycystic Ovarian Syndrome and Inhibits KGN Cell Proliferation via Targeting Insulin-Like Growth Factor 1 (IGF1)
Xiang, Yungai
Song, Yuxia
Li, Yan
Zhao, Dongmei
Ma, Liying
Tan, Li
MEDICAL SCIENCE MONITOR, 2016, 22 : 3383 - 3393
[4] Intrauterine Growth Restriction and Differential Patterns of Hepatic Growth and Expression of IGF1, PCK2, and HSDL1 mRNA in the Sheep Fetus in Late Gestation
Gentili, Sheridan
Morrison, Janna L.
McMillen, I. Caroline
BIOLOGY OF REPRODUCTION, 2009, 80 (06) : 1121 - 1127

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