MiR-194 Regulates the Proliferation and Migration Via Targeting Hnf1β in Mouse Metanephric Mesenchyme Cells

Overview

Journal In Vitro Cell Dev Biol Anim

Publisher Springer

Specialties Biology
Cell Biology

Date 2019 May 31

PMID 31144266

Citations 2

Authors

Yamin Liu

Yanxia Hu

Dongsheng Ni

Jianing Liu

Hua Xia

Lei Xu

Qin Zhou

Yajun Xie

Affiliations

Soon will be listed here.

Abstract

Hepatocyte nuclear factor-1β (Hnf1β) is associated with early embryogenesis failure, renal cysts, and/or diabetes. However, factors regulating Hnf1β expression in metanephric mesenchyme cells remain poorly understood. Here, we analyzed the modulation relationship of Hnf1β and miR-194 in mouse metanephric mesenchyme (MM) cells. Bioinformatics analysis, luciferase assay and semi-quantitative real-time (qPCR), western blotting, 5-ethynyl-2'-deoxyuridine cell proliferation assay, wound healing assay, and flow cytometry were employed to detect the function of miR-194 by targeting on Hnf1β in mouse MM cells. Bioinformatic prediction revealed one conserved binding site (CAGTATT) of miR-194 on Hnf1β 3'-UTR and luciferase reporter assay suggested that this is an effective target site of miR-194, and mutating CAGTATT with CGTACTT had no effects on luciferase activity compared with control. Overexpression of miR-194 decreased Hnf1β mRNA and protein level in mouse MM cells. In addition, miR-194-decreased cell proliferation and miR-194-promoted cell apoptosis and migration were reversed by overexpression of Hnf1β coding region. In addition, Hnf1β-upregulated genes were decreased in miR-194 overexpression cells and rescued in miR-194 and Hnf1β CDS region co-overexpression cells. Our findings explored one new regulator of Hnf1β and revealed the function of their regulation in cell proliferation, migration, and apoptosis in mouse metanephric mesenchyme cells. For strict regulation of Hnf1β in kidney development, these findings provide theoretical guidance for kidney development study and kidney disease therapy.

Citing Articles

Non-Coding RNAs in Hereditary Kidney Disorders.

Zhou J, Li X Int J Mol Sci. 2021; 22(6).

PMID: 33809516 PMC: 7998154. DOI: 10.3390/ijms22063014.

Eldecalcitol (ED-71)-induced exosomal miR-6887-5p suppresses squamous cell carcinoma cell growth by targeting heparin-binding protein 17/fibroblast growth factor-binding protein-1 (HBp17/FGFBP-1).

Higaki M, Shintani T, Hamada A, Rosli S, Okamoto T In Vitro Cell Dev Biol Anim. 2020; 56(3):222-233.

PMID: 32185608 DOI: 10.1007/s11626-020-00440-x.

References

Coffinier C, Barra J, Babinet C, Yaniv M . Expression of the vHNF1/HNF1beta homeoprotein gene during mouse organogenesis. Mech Dev. 1999; 89(1-2):211-3. DOI: 10.1016/s0925-4773(99)00221-x. View

Ambros V . The functions of animal microRNAs. Nature. 2004; 431(7006):350-5. DOI: 10.1038/nature02871. View

Sun Y, Koo S, White N, Peralta E, Esau C, Dean N . Development of a micro-array to detect human and mouse microRNAs and characterization of expression in human organs. Nucleic Acids Res. 2004; 32(22):e188. PMC: 545483. DOI: 10.1093/nar/gnh186. View

Dressler G . The cellular basis of kidney development. Annu Rev Cell Dev Biol. 2006; 22:509-29. DOI: 10.1146/annurev.cellbio.22.010305.104340. View

Kloosterman W, Plasterk R . The diverse functions of microRNAs in animal development and disease. Dev Cell. 2006; 11(4):441-50. DOI: 10.1016/j.devcel.2006.09.009. View

Dudziak K, Mottalebi N, Senkel S, Edghill E, Rosengarten S, Roose M . Transcription factor HNF1beta and novel partners affect nephrogenesis. Kidney Int. 2008; 74(2):210-7. DOI: 10.1038/ki.2008.149. View

Reidy K, Rosenblum N . Cell and molecular biology of kidney development. Semin Nephrol. 2009; 29(4):321-37. PMC: 2789488. DOI: 10.1016/j.semnephrol.2009.03.009. View

Lokmane L, Heliot C, Garcia-Villalba P, Fabre M, Cereghini S . vHNF1 functions in distinct regulatory circuits to control ureteric bud branching and early nephrogenesis. Development. 2009; 137(2):347-57. DOI: 10.1242/dev.042226. View

Bai X, Ma Y, Ding R, Fu B, Shi S, Chen X . miR-335 and miR-34a Promote renal senescence by suppressing mitochondrial antioxidative enzymes. J Am Soc Nephrol. 2011; 22(7):1252-61. PMC: 3137573. DOI: 10.1681/ASN.2010040367. View

10.

Ho J, Kreidberg J . The long and short of microRNAs in the kidney. J Am Soc Nephrol. 2012; 23(3):400-4. PMC: 3294314. DOI: 10.1681/ASN.2011080797. View

11.

Xu J, Kang Y, Liao W, Yu L . MiR-194 regulates chondrogenic differentiation of human adipose-derived stem cells by targeting Sox5. PLoS One. 2012; 7(3):e31861. PMC: 3291608. DOI: 10.1371/journal.pone.0031861. View

12.

Little M, McMahon A . Mammalian kidney development: principles, progress, and projections. Cold Spring Harb Perspect Biol. 2012; 4(5). PMC: 3331696. DOI: 10.1101/cshperspect.a008300. View

13.

Massa F, Garbay S, Bouvier R, Sugitani Y, Noda T, Gubler M . Hepatocyte nuclear factor 1β controls nephron tubular development. Development. 2013; 140(4):886-96. DOI: 10.1242/dev.086546. View

14.

Tang O, Chen X, Shen S, Hahn M, Pollock C . MiRNA-200b represses transforming growth factor-β1-induced EMT and fibronectin expression in kidney proximal tubular cells. Am J Physiol Renal Physiol. 2013; 304(10):F1266-73. DOI: 10.1152/ajprenal.00302.2012. View

15.

Sun K, Lai E . Adult-specific functions of animal microRNAs. Nat Rev Genet. 2013; 14(8):535-48. PMC: 4136762. DOI: 10.1038/nrg3471. View

16.

Lyu Z, Mao Z, Wang H, Fang Y, Chen T, Wan Q . MiR-181b targets Six2 and inhibits the proliferation of metanephric mesenchymal cells in vitro. Biochem Biophys Res Commun. 2013; 440(4):495-501. DOI: 10.1016/j.bbrc.2013.09.059. View

17.

Lv X, Mao Z, Lyu Z, Zhang P, Zhan A, Wang J . miR181c promotes apoptosis and suppresses proliferation of metanephric mesenchyme cells by targeting Six2 in vitro. Cell Biochem Funct. 2014; 32(7):571-9. DOI: 10.1002/cbf.3052. View

18.

Clissold R, Hamilton A, Hattersley A, Ellard S, Bingham C . HNF1B-associated renal and extra-renal disease-an expanding clinical spectrum. Nat Rev Nephrol. 2014; 11(2):102-12. DOI: 10.1038/nrneph.2014.232. View

19.

Lindstrom N, Lawrence M, Burn S, Johansson J, Bakker E, Ridgway R . Integrated β-catenin, BMP, PTEN, and Notch signalling patterns the nephron. Elife. 2015; 3:e04000. PMC: 4337611. DOI: 10.7554/eLife.04000. View

20.

Takasato M, Little M . The origin of the mammalian kidney: implications for recreating the kidney in vitro. Development. 2015; 142(11):1937-47. DOI: 10.1242/dev.104802. View