Long Non-coding RNA (lncRNA) Nuclear Enriched Abundant Transcript 1 (NEAT1) Regulates Fibroblast Growth Factor Receptor Substrate 2 (FRS2) by Targeting MicroRNA (miR)-29-3p in Hypertrophic Scar Fibroblasts

Overview

Journal Bioengineered

Date 2021 Aug 20

PMID 34414852

Citations 7

Authors

Qinghua Wu

Junjie Chen

Ziming Tan

Dehuai Wang

Jianwen Zhou

Dan Li

Ying Cen

Affiliations

Soon will be listed here.

Abstract

Long non-coding RNAs (lncRNAs) play crucial roles in human diseases. However, the detailed role of lncRNAs in hypertrophic scar fibroblasts (HSFs) is inadequately understood. This study aimed to investigate the potential role of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in hypertrophic scarring. Expression of lncRNAs, miRNAs, and genes were detected by polymerase chain reaction; protein expression was evaluated using western blotting. Cellular function was determined using the CCK-8 assay. The interaction between microRNA (miR)-29-3p and NEAT1 or fibroblast growth factor receptor substrate 2 (FRS2) was verified by luciferase and RNA pull-down assays. The results showed that NEAT1 was overexpressed in the hypertrophic dermis and in HSFs. However, knockdown of NEAT1 suppressed the proliferation and extracellular matrix (ECM) production of HSFs. Moreover, NEAT1 functioned as a competing endogenous RNA to upregulate FRS2 by sponging miR-29-3p. Downregulation of miR-29-3p or overexpression of FRS2 antagonized the effects of NEAT1 knockdown and promoted HSF proliferation and ECM release. In conclusion, NEAT1 knockdown protected against hypertrophic scarring by modulating the miR-29-3p/FRS2 axis, which is a viable target in scar treatment.

Citing Articles

Long non-coding RNA CRNDE promotes the progress of hypertrophic scar via regulating the proliferation and migration of hypertrophic scar fibroblasts through targeting microRNA-29a-3p.

Wang Z, Wu X, Zeng L Arch Dermatol Res. 2025; 317(1):440.

PMID: 39976754 DOI: 10.1007/s00403-025-03939-z.

Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Loaded Mir-29-3p Targets AhR to Improve Juvenile Idiopathic Arthritis via Inhibiting the Expression of IL-22 in CD4 T Cell.

Wei X, Sui K, Peng Y, Li S, Fang Y, Chen Z Stem Cell Rev Rep. 2024; 21(2):536-553.

PMID: 39621151 DOI: 10.1007/s12015-024-10827-y.

Hsa_circ_0032389 Enhances Proliferation and Migration in PDGF-BB-Induced Human Aortic Vascular Smooth Muscle Cells.

Qian H, Ma S, Zhou Q, Lei C Cardiovasc Toxicol. 2024; 24(2):111-121.

PMID: 38378972 DOI: 10.1007/s12012-024-09833-w.

SNHG1 functions as a ceRNA in hypertrophic scar fibroblast proliferation and apoptosis through miR-320b/CTNNB1 axis.

Li Q, Zhang B, Lu J, Wa Q, He M, Xie L Arch Dermatol Res. 2023; 315(6):1593-1601.

PMID: 36754869 DOI: 10.1007/s00403-022-02516-y.

Identifying miRNAs Associated with the Progression of Keloid through mRNA-miRNA Network Analysis and Validating the Targets of miR-29a-3p in Keloid Fibroblasts.

He Y, Zhang Z, Yin B, Li S, Wang P, Lan J Biomed Res Int. 2022; 2022:6487989.

PMID: 35872873 PMC: 9300312. DOI: 10.1155/2022/6487989.

References

Qian K, Liu G, Tang Z, Hu Y, Fang Y, Chen Z . The long non-coding RNA NEAT1 interacted with miR-101 modulates breast cancer growth by targeting EZH2. Arch Biochem Biophys. 2016; 615:1-9. DOI: 10.1016/j.abb.2016.12.011. View

Yang J, Deng P, Qi Y, Feng X, Wen H, Chen F . NEAT1 Knockdown Inhibits Keloid Fibroblast Progression by miR-196b-5p/FGF2 Axis. J Surg Res. 2020; 259:261-270. DOI: 10.1016/j.jss.2020.09.038. View

Zhao J, Zhou K, Ma L, Zhang H . MicroRNA-145 overexpression inhibits neuroblastoma tumorigenesis and . Bioengineered. 2020; 11(1):219-228. PMC: 7039631. DOI: 10.1080/21655979.2020.1729928. View

Cameron A, Adams D, Greenwood J, Anderson P, Cowin A . A novel murine model of hypertrophic scarring using subcutaneous infusion of bleomycin. Plast Reconstr Surg. 2013; 133(1):69-78. DOI: 10.1097/01.prs.0000436821.26709.a7. View

Jiang L, Huang J, Lu J, Hu S, Pei S, Ouyang Y . Ganoderma lucidum polysaccharide reduces melanogenesis by inhibiting the paracrine effects of keratinocytes and fibroblasts via IL-6/STAT3/FGF2 pathway. J Cell Physiol. 2019; 234(12):22799-22808. DOI: 10.1002/jcp.28844. View

Wu X, Li J, Yang X, Bai X, Shi J, Gao J . miR-155 inhibits the formation of hypertrophic scar fibroblasts by targeting HIF-1α via PI3K/AKT pathway. J Mol Histol. 2018; 49(4):377-387. DOI: 10.1007/s10735-018-9778-z. View

Ding N, Wu H, Tao T, Peng E . NEAT1 regulates cell proliferation and apoptosis of ovarian cancer by miR-34a-5p/BCL2. Onco Targets Ther. 2017; 10:4905-4915. PMC: 5640398. DOI: 10.2147/OTT.S142446. View

Mu S, Kang B, Zeng W, Sun Y, Yang F . MicroRNA-143-3p inhibits hyperplastic scar formation by targeting connective tissue growth factor CTGF/CCN2 via the Akt/mTOR pathway. Mol Cell Biochem. 2016; 416(1-2):99-108. DOI: 10.1007/s11010-016-2699-9. View

Rang Z, Wang Z, Pang Q, Wang Y, Yang G, Cui F . MiR-181a Targets PHLPP2 to Augment AKT Signaling and Regulate Proliferation and Apoptosis in Human Keloid Fibroblasts. Cell Physiol Biochem. 2016; 40(3-4):796-806. DOI: 10.1159/000453139. View

10.

Bartel D . MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116(2):281-97. DOI: 10.1016/s0092-8674(04)00045-5. View

11.

Calin G, Croce C . MicroRNA signatures in human cancers. Nat Rev Cancer. 2006; 6(11):857-66. DOI: 10.1038/nrc1997. View

12.

Sun H, Chen J, Qian W, Kang J, Wang J, Jiang L . Integrated long non-coding RNA analyses identify novel regulators of epithelial-mesenchymal transition in the mouse model of pulmonary fibrosis. J Cell Mol Med. 2016; 20(7):1234-46. PMC: 4929291. DOI: 10.1111/jcmm.12783. View

13.

Yu X, Li Z, Zheng H, Chan M, Wu W . NEAT1: A novel cancer-related long non-coding RNA. Cell Prolif. 2017; 50(2). PMC: 6529067. DOI: 10.1111/cpr.12329. View

14.

Wang X, Xu Y, Zhu Y, Wang Y, Li J, Li X . LncRNA NEAT1 promotes extracellular matrix accumulation and epithelial-to-mesenchymal transition by targeting miR-27b-3p and ZEB1 in diabetic nephropathy. J Cell Physiol. 2018; 234(8):12926-12933. DOI: 10.1002/jcp.27959. View

15.

Zhang Y, Zhang Y, Wang S, Li Q, Cao B, Huang B . SP1-induced lncRNA ZFPM2 antisense RNA 1 (ZFPM2-AS1) aggravates glioma progression via the miR-515-5p/Superoxide dismutase 2 (SOD2) axis. Bioengineered. 2021; 12(1):2299-2310. PMC: 8806534. DOI: 10.1080/21655979.2021.1934241. View

16.

Zhang Z, Li X, Liu Y, Zhang X, Li Y, Xu W . Recombinant human decorin inhibits cell proliferation and downregulates TGF-beta1 production in hypertrophic scar fibroblasts. Burns. 2007; 33(5):634-41. DOI: 10.1016/j.burns.2006.08.018. View

17.

Zhu Z, Ding J, Shankowsky H, Tredget E . The molecular mechanism of hypertrophic scar. J Cell Commun Signal. 2013; 7(4):239-52. PMC: 3889252. DOI: 10.1007/s12079-013-0195-5. View

18.

Zhu H, Bai W, Li C, Zheng Z, Guan H, Liu J . Knockdown of lncRNA-ATB suppresses autocrine secretion of TGF-β2 by targeting ZNF217 via miR-200c in keloid fibroblasts. Sci Rep. 2016; 6:24728. PMC: 4835760. DOI: 10.1038/srep24728. View

19.

Yang X, Zhang C, Jiang J, Li Y . Baicalein retards proliferation and collagen deposition by activating p38MAPK-JNK via microRNA-29. J Cell Biochem. 2019; 120(9):15625-15634. DOI: 10.1002/jcb.28829. View

20.

Lu T, Lin B, Li Y, Arora A, Han L, Cui C . Overexpression of microRNA-1 promotes cardiomyocyte commitment from human cardiovascular progenitors via suppressing WNT and FGF signaling pathways. J Mol Cell Cardiol. 2013; 63:146-54. PMC: 4268488. DOI: 10.1016/j.yjmcc.2013.07.019. View