Expression and Regulation of PIWIL-Proteins and PIWI-Interacting RNAs in Rheumatoid Arthritis

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2016 Nov 29

PMID 27893851

Citations 11

Authors

Lenka Plestilova

Michel Neidhart

Giancarlo Russo

Mojca Frank-Bertoncelj

Caroline Ospelt

Adrian Ciurea

Christoph Kolling

Renate E Gay

Beat A Michel

Jiri Vencovsky

Steffen Gay

Astrid Jungel

Affiliations

Soon will be listed here.

Abstract

Objective: The PIWIL (P-element induced wimpy testis like protein) subfamily of argonaute proteins is essential for Piwi-interacting RNA (piRNA) biogenesis and their function to silence transposons during germ-line development. Here we explored their presence and regulation in rheumatoid arthritis (RA).

Methods: The expression of PIWIL genes in RA and osteoarthritis (OA) synovial tissues and synovial fibroblasts (SF) was analysed by Real-time PCR, immunofluorescence and Western blot. The expression of piRNAs was quantified by next generation small RNA sequencing (NGS). The regulation of PIWI/piRNAs, proliferation and methylation of LINE-1 after silencing of PIWIL genes were studied.

Results: PIWIL2 and 4 mRNA were similarly expressed in synovial tissues and SF from RA and OA patients. However, on the protein level only PIWIL4 was strongly expressed in SF. Using NGS up to 300 piRNAs were identified in all SF without significant differences in expression levels between RA and OASF. Of interest, the analysis of the co-expression of the detected piRNAs revealed a less tightly regulated pattern of piRNA-823, -4153 and -16659 expression in RASF. In RASF and OASF, stimulation with TNFα+IL1β/TLR-ligands further significantly increased the expression levels of PIWIL2 and 4 mRNA and piRNA-16659 was significantly (4-fold) induced upon Poly(I:C) stimulation. Silencing of PIWIL2/4 neither affect LINE-1 methylation/expression nor proliferation of RASF.

Conclusion: We detected a new class of small regulatory RNAs (piRNAs) and their specific binding partners (PIWIL2/4) in synovial fibroblasts. The differential regulation of co-expression of piRNAs in RASF and the induction of piRNA/Piwi-proteins by innate immune stimulators suggest a role in inflammatory processes.

Citing Articles

piRNA associates with immune diseases.

Jiang M, Hong X, Gao Y, Kho A, Tantisira K, Li J Cell Commun Signal. 2024; 22(1):347.

PMID: 38943141 PMC: 11214247. DOI: 10.1186/s12964-024-01724-5.

Differential expression and correlation of immunoregulation related piRNA in rheumatoid arthritis.

Ren R, Tan H, Huang Z, Wang Y, Yang B Front Immunol. 2023; 14:1175924.

PMID: 37325646 PMC: 10266269. DOI: 10.3389/fimmu.2023.1175924.

The regulatory function of piRNA/PIWI complex in cancer and other human diseases: The role of DNA methylation.

Jia D, Jiang H, Zhang Y, Zhang Y, Qian L, Zhang Y Int J Biol Sci. 2022; 18(8):3358-3373.

PMID: 35637965 PMC: 9134905. DOI: 10.7150/ijbs.68221.

piRNAQuest V.2: an updated resource for searching through the piRNAome of multiple species.

Ghosh B, Sarkar A, Mondal S, Bhattacharya N, Khatua S, Ghosh Z RNA Biol. 2021; 19(1):12-25.

PMID: 34965192 PMC: 8786328. DOI: 10.1080/15476286.2021.2010960.

piRNA-36741 regulates BMP2-mediated osteoblast differentiation via METTL3 controlled m6A modification.

Liu J, Chen M, Ma L, Dang X, Du G Aging (Albany NY). 2021; 13(19):23361-23375.

PMID: 34645714 PMC: 8544320. DOI: 10.18632/aging.203630.

References

Chen C, Liu J, Xu G . Overexpression of PIWI proteins in human stage III epithelial ovarian cancer with lymph node metastasis. Cancer Biomark. 2014; 13(5):315-21. DOI: 10.3233/CBM-130360. View

Ross R, Weiner M, Lin H . PIWI proteins and PIWI-interacting RNAs in the soma. Nature. 2014; 505(7483):353-359. PMC: 4265809. DOI: 10.1038/nature12987. View

He X, Chen X, Zhang X, Duan X, Pan T, Hu Q . An Lnc RNA (GAS5)/SnoRNA-derived piRNA induces activation of TRAIL gene by site-specifically recruiting MLL/COMPASS-like complexes. Nucleic Acids Res. 2015; 43(7):3712-25. PMC: 4402533. DOI: 10.1093/nar/gkv214. View

Filkova M, Jungel A, Gay R, Gay S . MicroRNAs in rheumatoid arthritis: potential role in diagnosis and therapy. BioDrugs. 2012; 26(3):131-41. DOI: 10.2165/11631480-000000000-00000. View

Rajasethupathy P, Antonov I, Sheridan R, Frey S, Sander C, Tuschl T . A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity. Cell. 2012; 149(3):693-707. PMC: 3442366. DOI: 10.1016/j.cell.2012.02.057. View

Neidhart M, Karouzakis E, Schumann G, Gay R, Gay S . Trex-1 deficiency in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum. 2010; 62(9):2673-9. DOI: 10.1002/art.27567. View

Cui L, Lou Y, Zhang X, Zhou H, Deng H, Song H . Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using piRNAs as markers. Clin Biochem. 2011; 44(13):1050-1057. DOI: 10.1016/j.clinbiochem.2011.06.004. View

Peng L, Song L, Liu C, Lv X, Li X, Jie J . piR-55490 inhibits the growth of lung carcinoma by suppressing mTOR signaling. Tumour Biol. 2015; 37(2):2749-56. DOI: 10.1007/s13277-015-4056-0. View

Aradi B, Kato M, Filkova M, Karouzakis E, Klein K, Scharl M . Protein tyrosine phosphatase nonreceptor type 2: an important regulator of lnterleukin-6 production in rheumatoid arthritis synovial fibroblasts. Arthritis Rheumatol. 2015; 67(10):2624-33. DOI: 10.1002/art.39256. View

10.

Martinez V, Vucic E, Thu K, Hubaux R, Enfield K, Pikor L . Unique somatic and malignant expression patterns implicate PIWI-interacting RNAs in cancer-type specific biology. Sci Rep. 2015; 5:10423. PMC: 4444957. DOI: 10.1038/srep10423. View

11.

Kang H, Moon M, Lee H, Han S . Testosterone alters testis function through regulation of piRNA expression in rats. Mol Biol Rep. 2014; 41(10):6729-35. DOI: 10.1007/s11033-014-3558-y. View

12.

Neidhart M, Rethage J, Kuchen S, Kunzler P, Crowl R, Billingham M . Retrotransposable L1 elements expressed in rheumatoid arthritis synovial tissue: association with genomic DNA hypomethylation and influence on gene expression. Arthritis Rheum. 2001; 43(12):2634-47. DOI: 10.1002/1529-0131(200012)43:12<2634::AID-ANR3>3.0.CO;2-1. View

13.

Klareskog L, Catrina A, Paget S . Rheumatoid arthritis. Lancet. 2009; 373(9664):659-72. DOI: 10.1016/S0140-6736(09)60008-8. View

14.

Greither T, Koser F, Kappler M, Bache M, Lautenschlager C, Gobel S . Expression of human Piwi-like genes is associated with prognosis for soft tissue sarcoma patients. BMC Cancer. 2012; 12:272. PMC: 3472179. DOI: 10.1186/1471-2407-12-272. View

15.

Bamezai S, Rawat V, Buske C . Concise review: The Piwi-piRNA axis: pivotal beyond transposon silencing. Stem Cells. 2012; 30(12):2603-11. DOI: 10.1002/stem.1237. View

16.

Zhong F, Zhou N, Wu K, Guo Y, Tan W, Zhang H . A SnoRNA-derived piRNA interacts with human interleukin-4 pre-mRNA and induces its decay in nuclear exosomes. Nucleic Acids Res. 2015; 43(21):10474-91. PMC: 4666397. DOI: 10.1093/nar/gkv954. View

17.

Neumann E, Lefevre S, Zimmermann B, Gay S, Muller-Ladner U . Rheumatoid arthritis progression mediated by activated synovial fibroblasts. Trends Mol Med. 2010; 16(10):458-68. DOI: 10.1016/j.molmed.2010.07.004. View

18.

Su C, Ren Z, Wang F, Liu M, Li X, Tang H . PIWIL4 regulates cervical cancer cell line growth and is involved in down-regulating the expression of p14ARF and p53. FEBS Lett. 2012; 586(9):1356-62. DOI: 10.1016/j.febslet.2012.03.053. View

19.

Lakshmi S, Agrawal S . piRNABank: a web resource on classified and clustered Piwi-interacting RNAs. Nucleic Acids Res. 2007; 36(Database issue):D173-7. PMC: 2238943. DOI: 10.1093/nar/gkm696. View

20.

Arnett F, Edworthy S, Bloch D, McShane D, Fries J, Cooper N . The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988; 31(3):315-24. DOI: 10.1002/art.1780310302. View