Long non-coding RNA XIST promotes extracellular matrix degradation by functioning as a competing endogenous RNA of miR-1277-5p in osteoarthritis

Wang,Tao; Liu,Yize; Wang,Yong; Huang,Xuyang; Zhao,Wei; Zhao,Zhonghai

doi:10.3892/ijmm.2019.4240

Long non-coding RNA XIST promotes extracellular matrix degradation by functioning as a competing endogenous RNA of miR-1277-5p in osteoarthritis

Authors:
- Tao Wang
- Yize Liu
- Yong Wang
- Xuyang Huang
- Wei Zhao
- Zhonghai Zhao
View Affiliations

Affiliations: 4th Department of Orthopedic Surgery, Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China, 2nd Department of Neurology, Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China, Department of Rehabilitation, Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China
Published online on: June 12, 2019 https://doi.org/10.3892/ijmm.2019.4240
Pages: 630-642
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Osteoarthritis (OA) is a common and troublesome disease among the elderly, and is characterized by extracellular matrix (ECM) degradation. The function of the long non‑coding RNA X‑inactive‑specific transcript (XIST) and its working mechanism in ECM degradation remains unclear. In the present study, XIST was revealed to be upregulated in OA specimens and in articular chondrocytes (ACs) derived from OA tissue (AC/OA) and interleukin‑1β (IL‑1β)‑treated ACs. Loss‑of‑function experiments demonstrated that downregulation of XIST suppressed the degradation of the ECM in AC/OA and AC/IL‑1β‑5.0 cells. Furthermore, XIST, matrix metalloproteinase 13 (MMP‑13) and ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS5) were identified as targets of microRNA (miR)‑1277‑5p, and the reciprocal inhibitive effect between XIST and miR‑1277‑5p was elucidated. Furthermore, the role of XIST in ECM degradation was confirmed to be functioning as a competing endogenous RNA (ceRNA) of miR‑1277‑5p. Finally, the protective effect of the downregulation of XIST on ECM degradation was verified in an OA rat model. In conclusion, the present study suggests that XIST promotes MMP‑13 and ADAMTS5 expression, indicating ECM degradation, by functioning as a ceRNA of miR‑1277‑5p in OA. The present study proposed a novel potential target with a new working mechanism in molecular treating of OA.

View Figures

View References

1	van der Kraan PM: Osteoarthritis year 2012 in review: Biology. Osteoarthritis Cartilage. 20:1447–1450. 2012. View Article : Google Scholar : PubMed/NCBI
2	Mobasheri A: Osteoarthritis year 2012 in review: Biomarkers. Osteoarthritis Cartilage. 20:1451–1464. 2012. View Article : Google Scholar : PubMed/NCBI
3	Lee AS, Ellman MB, Yan D, Kroin JS, Cole BJ, van Wijnen AJ and Im HJ: A current review of molecular mechanisms regarding osteoarthritis and pain. Gene. 527:440–447. 2013. View Article : Google Scholar : PubMed/NCBI
4	Sofat N: Analysing the role of endogenous matrix molecules in the development of osteoarthritis. Int J Exp Pathol. 90:463–479. 2009. View Article : Google Scholar : PubMed/NCBI
5	Verma P and Dalal K: ADAMTS-4 and ADAMTS-5: Key enzymes in osteoarthritis. J Cell Biochem. 112:3507–3514. 2011. View Article : Google Scholar : PubMed/NCBI
6	Chen WX, Shan FJ, Jin HT, Wang PE, Xiao LW and Tong PJ: Research on application of determination of MMP-13 in osteoarthritis. Zhongguo Gu Shang. 27:617–620. 2014.In Chinese. PubMed/NCBI
7	Huynh NP, Anderson BA, Guilak F and McAlinden A: Emerging roles for long noncoding RNAs in skeletal biology and disease. Connect Tissue Res. 58:116–141. 2017. View Article : Google Scholar :
8	Jiang SD, Lu J, Deng ZH, Li YS and Lei GH: Long noncoding RNAs in osteoarthritis. Joint Bone Spine. 84:553–556. 2017. View Article : Google Scholar
9	Hu Y, Deng C, Zhang H, Zhang J, Peng B and Hu C: Long non-coding RNA XIST promotes cell growth and metastasis through regulating miR-139-5p mediated Wnt/β-catenin signaling pathway in bladder cancer. Oncotarget. 8:94554–94568. 2017.PubMed/NCBI
10	Sun N, Zhang G and Liu Y: Long non-coding RNA XIST sponges miR-34a to promotes colon cancer progression via Wnt/β-catenin signaling pathway. Gene. 665:141–148. 2018. View Article : Google Scholar : PubMed/NCBI
11	Zheng R, Lin S, Guan L, Yuan H, Liu K, Liu C, Ye W, Liao Y, Jia J and Zhang R: Long non-coding RNA XIST inhibited breast cancer cell growth, migration, and invasion via miR-155/CDX1 axis. Biochem Biophys Res Commun. 498:1002–1008. 2018. View Article : Google Scholar : PubMed/NCBI
12	Zhou Q, Hu W, Zhu W, Zhang F, Lin-Lin L, Liu C, Songyang YY, Sun CC and Li D: Long non coding RNA XIST as a prognostic cancer marker - A meta-analysis. Clin Chim Acta. 482:1–7. 2018. View Article : Google Scholar : PubMed/NCBI
13	Fu M, Huang G, Zhang Z, Liu J, Zhang Z, Huang Z, Yu B and Meng F: Expression profile of long noncoding RNAs in cartilage from knee osteoarthritis patients. Osteoarthritis Cartilage. 23:423–432. 2015. View Article : Google Scholar
14	Denzler R, Agarwal V, Stefano J, Bartel DP and Stoffel M: Assessing the ceRNA hypothesis with quantitative measurements of miRNA and target abundance. Mol Cell. 54:766–776. 2014. View Article : Google Scholar : PubMed/NCBI
15	Kanduri C: Long noncoding RNAs: Lessons from genomic imprinting. Biochim Biophys Acta. 1859:102–111. 2016. View Article : Google Scholar
16	Mondal T, Subhash S, Vaid R, Enroth S, Uday S, Reinius B, Mitra S, Mohammed A, James AR, Hoberg E, et al: MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA-DNA triplex structures. Nat Commun. 6:77432015. View Article : Google Scholar
17	Wang C, Wang L, Ding Y, Lu X, Zhang G, Yang J, Zheng H, Wang H, Jiang Y and Xu L: LncRNA structural characteristics in epigenetic regulation. Int J Mol Sci. 18:2017. View Article : Google Scholar
18	Yuan SX, Zhang J, Xu QG, Yang Y and Zhou WP: Long noncoding RNA, the methylation of genomic elements and their emerging crosstalk in hepatocellular carcinoma. Cancer Lett. 379:239–244. 2016. View Article : Google Scholar
19	Zampetaki A and Mayr M: Long noncoding RNAs and angiogenesis: Regulatory information for chromatin remodeling. Circulation. 136:80–82. 2017. View Article : Google Scholar : PubMed/NCBI
20	Salmena L, Poliseno L, Tay Y, Kats L and Pandolfi PP: A ceRNA hypothesis: The Rosetta Stone of a hidden RNA language? Cell. 146:353–358. 2011. View Article : Google Scholar : PubMed/NCBI
21	Gu S, Xie R, Liu X, Shou J, Gu W and Che X: Long coding RNA XIST contributes to neuronal apoptosis through the downregulation of AKT phosphorylation and is negatively regulated by miR-494 in rat spinal cord injury. Int J Mol Sci. 18:2017. View Article : Google Scholar
22	Zhang R and Xia T: Long non-coding RNA XIST regulates PDCD4 expression by interacting with miR-21-5p and inhibits osteosarcoma cell growth and metastasis. Int J Oncol. 51:1460–1470. 2017. View Article : Google Scholar : PubMed/NCBI
23	Gosset M, Berenbaum F, Thirion S and Jacques C: Primary culture and phenotyping of murine chondrocytes. Nat Protoc. 3:1253–1260. 2008. View Article : Google Scholar : PubMed/NCBI
24	Wang Y, Yang T, Liu Y, Zhao W, Zhang Z, Lu M and Zhang W: Decrease of miR-195 promotes chondrocytes proliferation and maintenance of chondrogenic phenotype via targeting FGF-18 pathway. Int J Mol Sci. 18:2017.
25	Li YF, Li SH, Liu Y and Luo YT: Long noncoding RNA CIR promotes chondrocyte extracellular matrix degradation in osteoarthritis by acting as a sponge for Mir-27b. Cell Physiol Biochem. 43:602–610. 2017. View Article : Google Scholar : PubMed/NCBI
26	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar
27	Cai H, Liu X, Zheng J, Xue Y, Ma J, Li Z, Xi Z, Li Z, Bao M and Liu Y: Long non-coding RNA taurine upregulated 1 enhances tumor-induced angiogenesis through inhibiting microRNA-299 in human glioblastoma. Oncogene. 36:318–331. 2017. View Article : Google Scholar
28	Glasson SS, Blanchet TJ and Morris EA: The surgical destabilization of the medial meniscus (DMM) model of osteoarthritis in the 129/SvEv mouse. Osteoarthritis Cartilage. 15:1061–1069. 2007. View Article : Google Scholar : PubMed/NCBI
29	Wang Y, Zhang Y, Yang T, Zhao W, Wang N, Li P, Zeng X and Zhang W: Long non-coding RNA MALAT1 for promoting metastasis and proliferation by acting as a ceRNA of miR-144-3p in osteosarcoma cells. Oncotarget. 8:59417–59434. 2017.PubMed/NCBI
30	Hoff P, Buttgereit F, Burmester GR, Jakstadt M, Gaber T, Andreas K, Matziolis G, Perka C and Röhner E: Osteoarthritis synovial fluid activates pro-inflammatory cytokines in primary human chondrocytes. Int Orthop. 37:145–151. 2013. View Article : Google Scholar :
31	Chowdhury TT, Schulz RM, Rai SS, Thuemmler CB, Wuestneck N, Bader A and Homandberg GA: Biomechanical modulation of collagen fragment-induced anabolic and catabolic activities in chondrocyte/agarose constructs. Arthritis Res Ther. 12:R822010. View Article : Google Scholar : PubMed/NCBI
32	Di Pizio A, Agamennone M and Tortorella P: Non-Zinc-binding inhibitors of MMP-13: GRID-based approaches to rationalize the binding process. Curr Top Med Chem. 16:449–459. 2016. View Article : Google Scholar
33	Li H, Wang D, Yuan Y and Min J: New insights on the MMP-13 regulatory network in the pathogenesis of early osteoarthritis. Arthritis Res Ther. 19:2482017. View Article : Google Scholar : PubMed/NCBI
34	Xie XW, Wan RZ and Liu ZP: Recent research advances in selective matrix metalloproteinase-13 inhibitors as anti-osteoarthritis agents. ChemMedChem. 12:1157–1168. 2017. View Article : Google Scholar : PubMed/NCBI
35	Apte SS: Anti-ADAMTS5 monoclonal antibodies: Implications for aggrecanase inhibition in osteoarthritis. Biochem J. 473:e1–e4. 2016. View Article : Google Scholar
36	Bondeson J, Wainwright S, Hughes C and Caterson B: The regulation of the ADAMTS4 and ADAMTS5 aggrecanases in osteoarthritis: A review. Clin Exp Rheumatol. 26:139–145. 2008.PubMed/NCBI
37	Tortorella MD, Burn TC, Pratta MA, Abbaszade I, Hollis JM, Liu R, Rosenfeld SA, Copeland RA, Decicco CP, Wynn R, et al: Purification and cloning of aggrecanase-1: A member of the ADAMTS family of proteins. Science. 284:1664–1666. 1999. View Article : Google Scholar : PubMed/NCBI
38	Zeng W, Corcoran C, Collins-Racie LA, Lavallie ER, Morris EA and Flannery CR: Glycosaminoglycan-binding properties and aggrecanase activities of truncated ADAMTSs: Comparative analyses with ADAMTS-5, -9, -16 and -18. Biochim Biophys Acta. 1760:517–524. 2006. View Article : Google Scholar : PubMed/NCBI
39	Budak F, Bal SH, Tezcan G, Akalın H, Goral G and Oral HB: Altered expressions of miR-1238-3p miR-494, miR-6069, and miR-139-3p in the formation of chronic brucellosis. J Immunol Res. 2016:45914682016. View Article : Google Scholar
40	Motieghader H, Kouhsar M, Najafi A, Sadeghi B and Masoudi-Nejad A: mRNA-miRNA bipartite network reconstruction to predict prognostic module biomarkers in colorectal cancer stage differentiation. Mol Biosyst. 13:2168–2180. 2017. View Article : Google Scholar : PubMed/NCBI
41	Crowe N, Swingler TE, Le LT, Barter MJ, Wheeler G, Pais H, Donell ST, Young DA, Dalmay T and Clark IM: Detecting new microRNAs in human osteoarthritic chondrocytes identifies miR-3085 as a human, chondrocyte-selective, microRNA. Osteoarthritis Cartilage. 24:534–543. 2016. View Article : Google Scholar :
42	Nugent M: MicroRNAs: Exploring new horizons in osteoarthritis. Osteoarthritis Cartilage. 24:573–580. 2016. View Article : Google Scholar
43	Sondag GR and Haqqi TM: The role of MicroRNAs and their targets in osteoarthritis. Curr Rheumatol Rep. 18:562016. View Article : Google Scholar : PubMed/NCBI
44	Zhang M, Lygrisse K and Wang J: Role of MicroRNA in osteoarthritis. J Arthritis. 6:2017. View Article : Google Scholar : PubMed/NCBI
45	Kopańska M, Szala D, Czech J, Gabło N, Gargasz K, Trzeciak M, Zawlik I and Snela S: MiRNA expression in the cartilage of patients with osteoarthritis. J Orthop Surg Res. 12:512017. View Article : Google Scholar
46	Peffers MJ, Balaskas P and Smagul A: Osteoarthritis year in review 2017: Genetics and epigenetics. Osteoarthritis Cartilage. 26:304–311. 2018. View Article : Google Scholar
47	Zhang HD, Jiang LH, Sun DW, Hou JC and Ji ZL: CircRNA: A novel type of biomarker for cancer. Breast Cancer. 25:1–7. 2018. View Article : Google Scholar
48	Zhao C, Wang Y, Jin H and Yu T: Knockdown of microRNA-203 alleviates LPS-induced injury by targeting MCL-1 in C28/I2 chondrocytes. Exp Cell Res. 359:171–178. 2017. View Article : Google Scholar : PubMed/NCBI
49	Li C, Wan L, Liu Z, Xu G, Wang S, Su Z, Zhang Y, Zhang C, Liu X, Lei Z and Zhang HT: Long non-coding RNA XIST promotes TGF-β-induced epithelial-mesenchymal transition by regulating miR-367/141-ZEB2 axis in non-small-cell lung cancer. Cancer Lett. 418:185–195. 2018. View Article : Google Scholar : PubMed/NCBI
50	Liu X, Cui L and Hua D: Long non-coding RNA XIST regulates miR-137-EZH2 axis to promote tumor metastasis in colorectal cancer. Oncol Res. 27:99–106. 2018. View Article : Google Scholar : PubMed/NCBI
51	Sun Z, Zhang B and Cui T: Long non-coding RNA XIST exerts oncogenic functions in pancreatic cancer via miR-34a-5p. Oncol Rep. 39:1591–1600. 2018.PubMed/NCBI
52	Yang C, Wu K, Wang S and Wei G: Long non-coding RNA XIST promotes osteosarcoma progression by targeting YAP via miR-195-5p. J Cell Biochem. 119:5646–5656. 2018. View Article : Google Scholar : PubMed/NCBI
53	Li Y, Li S, Luo Y, Liu Y and Yu N: LncRNA PVT1 regulates chondrocyte apoptosis in osteoarthritis by acting as a sponge for miR-488-3p. DNA Cell Biol. 36:571–580. 2017. View Article : Google Scholar : PubMed/NCBI