The scinderin gene (SCIN) is the direct target of miR3085-3p in chondrocytes

Authors

Keywords:

chondrocyte, miR-3085-3p, osteoarthritis, SCIN

Abstract

Paper description:

  • Aberrant expression of miR-3085-3p is found in osteoarthritis (OA). Insight into its biological function could be useful for future miRNA-based therapy of OA. miRNA biological function can be dictated through its direct targets.
  • Bioinformatic algorithms were employed to identify miRNA potential targets. The target was then verified experimentally.
  • The gene scinderin (SCIN) is the direct target for miRNA-3085-3p in chondrocytes, the only cell in cartilage.
  • MiR-3085-3p might play a role in OA at least in part through direct targeting of SCIN.


Abstract: MiR-3085-3p was shown to play a crucial role in cartilage biology, with potential impacts in osteoarthritis (OA). Insight into this miRNA function could be of practical importance for future miRNA-based therapy, however, little is known regarding the biological roles of this miRNA. The physiologic function of an individual miRNA is dictated through its mRNA targets, and as SCIN (scinderin, also known as adseverin) was reported to be involved in chondrocyte differentiation, maturation, and phenotype maintenance, this study aimed to prove SCIN is a direct target of miRNA-3085-3p. Bioinformatics algorithms were utilized for predicting their interacting sites. Gain- and loss-of-function experiments with miRNA-3085-3p were performed and SCIN expression was measured by real-time RT-PCR. SCIN 3'UTR regions harboring either the miR-3085-3p seed site or its mutant version were cloned into pmirGLO downstream of a reporter firefly luciferase encoding gene. The effect of miR-3085-3p on this region was determined by the luciferase assay. Four binding sites of miR-3085-3p in SCIN 3'UTR were identified. SCIN expression level was found to be inversely correlated with the level of miRNA-3085-3p. MiR3085-3p directly binds to its binding sites in SCIN 3' UTR. These data suggest that SCIN is the direct target of miR-3085-3p in chondrocyte cells.

https://doi.org/10.2298/ABS200507031L

Received: May 7, 2020; Revised: July 15, 2020; Accepted: August 1, 2020; Published online: August 24, 2020

How to cite this article: Le LT, Ho PT, Clark IM.The scinderin gene (SCIN) is the direct target of miR3085-3p in chondrocytes. Arch Biol Sci. 2020;72(3):373-8.

Downloads

Download data is not yet available.

References

Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281-97.

He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5(7):522.

Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120(1):15-20.

Dweep H, Sticht C, Gretz N. In-silico algorithms for the screening of possible microRNA binding sites and their interactions. Curr Genomics. 2013;14(2):127-36.

Riffo-Campos ÁL, Riquelme I, Brebi-Mieville P. Tools for sequence-based miRNA target prediction: what to choose? Int J Mol Sci. 2016;17(12):1987.

Saito T, Sætrom P. MicroRNAs–targeting and target prediction. N Biotechnol. 2010;27(3):243-9.

Didiano D, Hobert O. Perfect seed pairing is not a generally reliable predictor for miRNA-target interactions. Nat Struct Mol Biol. 2006;13(9):849-51.

M Witkos T, Koscianska E, J Krzyzosiak W. Practical aspects of microRNA target prediction. Curr Mol Med. 2011;11(2):93-109.

Crowe N, Swingler T, Le L, Barter M, Wheeler G, Pais H, Donell S, Young D, Dalmay T, Clark I. Detecting new microRNAs in human osteoarthritic chondrocytes identifies miR-3085 as a human, chondrocyte-selective, microRNA. Osteoarthr Cartil. 2016;24(3):534-43.

Cao Y, Wang Y, Sprangers S, Picavet DI, Glogauer M, McCulloch CA, Everts V. Deletion of adseverin in osteoclasts affects cell structure but not bone metabolism. Calcif Tissue Int. 2017;101(2):207-16.

Chan B, Parreno J, Glogauer M, Wang Y, Kandel R. Adseverin, an actin binding protein, regulates articular chondrocyte phenotype. J Tissue Eng Regen Med. 2019;13(8):1438-52.

Nurminsky D, Magee C, Faverman L, Nurminskaya M. Regulation of chondrocyte differentiation by actin-severing protein adseverin. Dev Biol. 2007;302(2):427-37.

Rai MF, Patra D, Sandell LJ, Brophy RH. Transcriptome analysis of injured human meniscus reveals a distinct phenotype of meniscus degeneration with aging. Arthritis Rheum. 2013;65(8):2090-101.

Brennecke J, Stark A, Russell RB, Cohen SM. Principles of microRNA–target recognition. PLoS Biol. 2005;3(3).

Catalanotto C, Cogoni C, Zardo G. MicroRNA in control of gene expression: an overview of nuclear functions. Int J Mol Sci. 2016;17(10):1712.

Shivdasani RA. MicroRNAs: regulators of gene expression and cell differentiation. Blood. 2006;108(12):3646-53.

Ardekani AM, Naeini MM. The role of microRNAs in human diseases. Avicenna J Med Biotechnol. 2010;2(4):161.

Ha T-Y. MicroRNAs in human diseases: from cancer to cardiovascular disease. Immune Netw. 2011;11(3):135-54.

Jones S, Watkins G, Le Good N, Roberts S, Murphy C, Brockbank S, Needham M, Read S, Newham P. The identification of differentially expressed microRNA in osteoarthritic tissue that modulate the production of TNF-α and MMP13. Osteoarthr Cartil. 2009;17(4):464-72.

Iliopoulos D, Malizos KN, Oikonomou P, Tsezou A. Integrative microRNA and proteomic approaches identify novel osteoarthritis genes and their collaborative metabolic and inflammatory networks. PLoS One. 2008;3(11):e3740.

Díaz-Prado S, Cicione C, Muiños-López E, Hermida-Gómez T, Oreiro N, Fernández-López C, Blanco FJ. Characterization of microRNA expression profiles in normal and osteoarthritic human chondrocytes. BMC Musculoskelet Disord. 2012;13(1):144.

Downloads

Published

2020-10-19

How to Cite

1.
Le LT, Ho PT, Clark IM. The scinderin gene (SCIN) is the direct target of miR3085-3p in chondrocytes. Arch Biol Sci [Internet]. 2020Oct.19 [cited 2024Mar.29];72(3):373-8. Available from: https://serbiosoc.org.rs/arch/index.php/abs/article/view/5340

Issue

Section

Articles