Integrated Analysis of Long Non-coding RNAs and MRNAs Associated with Peritendinous Fibrosis

Overview

Journal J Adv Res

Specialties General Medicine
Science

Date 2018 Dec 25

PMID 30581612

Citations 14

Authors

Wei Zheng

Chen Chen

Shuai Chen

Cunyi Fan

Hongjiang Ruan

Affiliations

Soon will be listed here.

Abstract

The dysregulation of long non-coding RNAs (lncRNAs) is associated with the development of various diseases. However, little is known about the regulatory function of lncRNAs in peritendinous fibrosis. Therefore, the expression profiles of lncRNAs and mRNAs in normal tendon and fibrotic peritendinous tissues were analyzed in this study using RNA sequencing. In total, 219 lncRNAs and 3403 mRNAs were identified that were differentially expressed between the two sets of tissues. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that the dysregulated mRNAs were mainly associated with immune regulation, inflammation, extracellular matrix (ECM) production and remodeling, and cell cycle regulation. An lncRNA-mRNA co-expression network revealed 181 network pairs comprising eight dysregulated lncRNAs and 146 mRNAs. The results of the bioinformatics analysis indicated that the dysregulated lncRNAs play a role in fibrogenesis through regulation of the cell cycle, inflammation, and ECM production. Furthermore, silencing the lncRNA dnm3os prevented transforming growth factor (TGF)-β1-induced tenocyte proliferation and expression of genes related to fibrogenesis. These findings provide a basis for investigations into the regulatory mechanisms underlying the development and progression of peritendinous fibrosis.

Citing Articles

RNA-seq profiling identified a three-lncRNA panel in serum as potential biomarker for muscle-invasive bladder cancer.

Jiang X, Qu A, Zhang S, Jin S, Wang L, Zhang Y Front Oncol. 2024; 14:1451009.

PMID: 39737397 PMC: 11683095. DOI: 10.3389/fonc.2024.1451009.

Human Tendon-on-a-Chip for Modeling the Myofibroblast Microenvironment in Peritendinous Fibrosis.

Ajalik R, Linares I, Alenchery R, Zhang V, Wright T, Miller B Adv Healthc Mater. 2024; 14(4):e2403116.

PMID: 39544139 PMC: 11804843. DOI: 10.1002/adhm.202403116.

RMRP accelerates ligamentum flavum hypertrophy by regulating GSDMD-mediated pyroptosis through Gli1 SUMOylation.

Yan X, Liu T, Zhang R, Ma Q, Sun C Front Immunol. 2024; 15:1427970.

PMID: 39221246 PMC: 11362830. DOI: 10.3389/fimmu.2024.1427970.

Long Non-coding RNA DNM3OS: Pathogenic Roles and Molecular Mechanisms in Pathophysiological Processes.

Wang S, Hu Y, Wang R, Zhang Y, Yuan Q, Yuan C Curr Med Chem. 2024; 31(29):4687-4702.

PMID: 39081025 DOI: 10.2174/0109298673280484240101070607.

Advances in non-coding RNA in tendon injuries.

Wang B, Chen Q, Zou X, Zheng P, Zhu J Front Genet. 2024; 15:1396195.

PMID: 38836038 PMC: 11148651. DOI: 10.3389/fgene.2024.1396195.

References

Marshall A, Rushbrook S, Morris L, Scott I, Vowler S, Davies S . Hepatocyte expression of minichromosome maintenance protein-2 predicts fibrosis progression after transplantation for chronic hepatitis C virus: a pilot study. Liver Transpl. 2005; 11(4):427-33. DOI: 10.1002/lt.20347. View

Helskov Jorgensen L, Jensen C, Wewer U, Schroder H . Transgenic overexpression of ADAM12 suppresses muscle regeneration and aggravates dystrophy in aged mdx mice. Am J Pathol. 2007; 171(5):1599-607. PMC: 2043520. DOI: 10.2353/ajpath.2007.070435. View

Gaggar A, Jackson P, Noerager B, OReilly P, McQuaid D, Rowe S . A novel proteolytic cascade generates an extracellular matrix-derived chemoattractant in chronic neutrophilic inflammation. J Immunol. 2008; 180(8):5662-9. PMC: 3998665. DOI: 10.4049/jimmunol.180.8.5662. View

Chuang L, Teixeira L, Wohlschlegel J, Henze M, Yates J, Mendez J . Phosphorylation of Mcm2 by Cdc7 promotes pre-replication complex assembly during cell-cycle re-entry. Mol Cell. 2009; 35(2):206-16. PMC: 2725784. DOI: 10.1016/j.molcel.2009.06.014. View

Kudo A . Periostin in fibrillogenesis for tissue regeneration: periostin actions inside and outside the cell. Cell Mol Life Sci. 2011; 68(19):3201-7. PMC: 3173633. DOI: 10.1007/s00018-011-0784-5. View

Taniguchi T, Asano Y, Akamata K, Aozasa N, Noda S, Takahashi T . Serum levels of ADAM12-S: possible association with the initiation and progression of dermal fibrosis and interstitial lung disease in patients with systemic sclerosis. J Eur Acad Dermatol Venereol. 2012; 27(6):747-53. DOI: 10.1111/j.1468-3083.2012.04558.x. View

Wynn T, Ramalingam T . Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat Med. 2012; 18(7):1028-40. PMC: 3405917. DOI: 10.1038/nm.2807. View

Novikova I, Hennelly S, Tung C, Sanbonmatsu K . Rise of the RNA machines: exploring the structure of long non-coding RNAs. J Mol Biol. 2013; 425(19):3731-46. DOI: 10.1016/j.jmb.2013.02.030. View

Kerna I, Kisand K, Suutre S, Murde M, Tamm A, Kumm J . The ADAM12 is upregulated in synovitis and postinflammatory fibrosis of the synovial membrane in patients with early radiographic osteoarthritis. Joint Bone Spine. 2013; 81(1):51-6. DOI: 10.1016/j.jbspin.2013.03.007. View

10.

Juneja S, Schwarz E, OKeefe R, Awad H . Cellular and molecular factors in flexor tendon repair and adhesions: a histological and gene expression analysis. Connect Tissue Res. 2013; 54(3):218-26. PMC: 3697755. DOI: 10.3109/03008207.2013.787418. View

11.

Azzouzi H, Leptidis S, Dirkx E, Hoeks J, van Bree B, Brand K . The hypoxia-inducible microRNA cluster miR-199a∼214 targets myocardial PPARδ and impairs mitochondrial fatty acid oxidation. Cell Metab. 2013; 18(3):341-54. DOI: 10.1016/j.cmet.2013.08.009. View

12.

Hernandez V, Weng J, Ly P, Pompey S, Dong H, Mishra L . Cavin-3 dictates the balance between ERK and Akt signaling. Elife. 2013; 2:e00905. PMC: 3780650. DOI: 10.7554/eLife.00905. View

13.

Krawczyk M, Emerson B . p50-associated COX-2 extragenic RNA (PACER) activates COX-2 gene expression by occluding repressive NF-κB complexes. Elife. 2014; 3:e01776. PMC: 4017649. DOI: 10.7554/eLife.01776. View

14.

Jiang S, Zhao X, Chen S, Pan G, Song J, He N . Down-regulating ERK1/2 and SMAD2/3 phosphorylation by physical barrier of celecoxib-loaded electrospun fibrous membranes prevents tendon adhesions. Biomaterials. 2014; 35(37):9920-9929. DOI: 10.1016/j.biomaterials.2014.08.028. View

15.

Yarmishyn A, Batagov A, Tan J, Sundaram G, Sampath P, Kuznetsov V . HOXD-AS1 is a novel lncRNA encoded in HOXD cluster and a marker of neuroblastoma progression revealed via integrative analysis of noncoding transcriptome. BMC Genomics. 2014; 15 Suppl 9:S7. PMC: 4290621. DOI: 10.1186/1471-2164-15-S9-S7. View

16.

Meng X, Tang P, Li J, Lan H . TGF-β/Smad signaling in renal fibrosis. Front Physiol. 2015; 6:82. PMC: 4365692. DOI: 10.3389/fphys.2015.00082. View

17.

Darby I, Zakuan N, Billet F, Desmouliere A . The myofibroblast, a key cell in normal and pathological tissue repair. Cell Mol Life Sci. 2015; 73(6):1145-57. PMC: 11108523. DOI: 10.1007/s00018-015-2110-0. View

18.

Li H, Peng X, Wang Y, Cao S, Xiong L, Fan J . Atg5-mediated autophagy deficiency in proximal tubules promotes cell cycle G2/M arrest and renal fibrosis. Autophagy. 2016; 12(9):1472-86. PMC: 5082781. DOI: 10.1080/15548627.2016.1190071. View

19.

Ashley S, Wilke C, Kim K, Moore B . Periostin regulates fibrocyte function to promote myofibroblast differentiation and lung fibrosis. Mucosal Immunol. 2016; 10(2):341-351. PMC: 5250615. DOI: 10.1038/mi.2016.61. View

20.

Meng X, Wang S, Huang X, Yang C, Xiao J, Zhang Y . Inflammatory macrophages can transdifferentiate into myofibroblasts during renal fibrosis. Cell Death Dis. 2016; 7(12):e2495. PMC: 5261004. DOI: 10.1038/cddis.2016.402. View