lncRNA WT1‑AS is upregulated in osteoporosis and regulates the apoptosis of osteoblasts by interacting with p53

Wang,Chaoqun; Xie,Quan; Sun,Wen; Zhou,Ying; Liu,Yu

doi:10.3892/etm.2021.10166

lncRNA WT1‑AS is upregulated in osteoporosis and regulates the apoptosis of osteoblasts by interacting with p53

Authors:
- Chaoqun Wang
- Quan Xie
- Wen Sun
- Ying Zhou
- Yu Liu
View Affiliations

Affiliations: Department of Nuclear Medicine, Hainan General Hospital, Haikou, Hainan 570311, P.R. China, Department of Nuclear Medicine, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570100, P.R. China, Cancer Institute Of Hainan Medicail University, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570100, P.R. China
Published online on: May 9, 2021 https://doi.org/10.3892/etm.2021.10166
Article Number: 734
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

In cervical cancer, cellular tumor antigen p53 (p53) interacts with long non‑coding WT1 antisense RNA (WT1‑AS) and this protein serves an important role in osteoporosis. The present study aimed to investigate the role of WT1‑AS in osteoporosis. WT1‑AS was upregulated in the plasma of patients with osteoporosis and was positively correlated with p53 expression. Altered expression of WT1‑AS and p53 separated patients with osteoporosis from healthy controls. Expression levels of WT1‑AS and p53 decreased with prolonged treatment. In osteoblasts, WT1‑AS overexpression resulted in increased p53 expression, while WT1‑AS small interfering RNA (siRNA) silencing resulted in decreased p53 expression. In addition, WT1‑AS overexpression resulted in increased apoptosis rate, while WT1‑AS siRNA silencing resulted in decreased apoptosis rate in osteoblasts. p53 overexpression attenuated the effects of WT1‑AS siRNA silencing on cell apoptosis. Therefore, WT1‑AS was upregulated during osteoporosis and regulated the apoptosis of osteoblasts by interacting with p53.

View Figures

View References

1	Siris ES, Adler R, Bilezikian J, Bolognese M, Dawson-Hughes B, Favus MJ, Harris ST, Jan de Beur SM, Khosla S, Lane NE, et al: The clinical diagnosis of osteoporosis: A position statement from the National Bone Health Alliance Working Group. Osteoporos Int. 25:1439–1443. 2014.PubMed/NCBI View Article : Google Scholar
2	Khosla S and Hofbauer LC: Osteoporosis treatment: Recent developments and ongoing challenges. Lancet Diabetes Endocrinol. 5:898–907. 2017.PubMed/NCBI View Article : Google Scholar
3	Lötters FJB, van den Bergh JP, de Vries F and Rutten-van Mölken MP: Current and future incidence and costs of osteoporosis-related fractures in the Netherlands: Combining claims data with BMD measurements. Calcif Tissue Int. 98:235–243. 2016.PubMed/NCBI View Article : Google Scholar
4	Curtis EM, Moon RJ, Dennison EM, Harvey NC and Cooper C: Recent advances in the pathogenesis and treatment of osteoporosis. Clin Med (Lond). 15 (Suppl 6):S92–S96. 2015.PubMed/NCBI View Article : Google Scholar
5	Raisz LG: Pathogenesis of osteoporosis: Concepts, conflicts, and prospects. J Clin Invest. 115:3318–3325. 2005.PubMed/NCBI View Article : Google Scholar
6	Reyes J, Chen JY, Stewart-Ornstein J, Karhohs KW, Mock CS and Lahav G: Fluctuations in p53 signaling allow escape from cell-cycle arrest. Mol Cell. 2018. 71:581–591. e5. 2018.PubMed/NCBI View Article : Google Scholar
7	Willms A, Schittek H, Rahn S, Sosna J, Mert U, Adam D and Trauzold A: Impact of p53 status on TRAIL-mediated apoptotic and non-apoptotic signaling in cancer cells. PLoS One. 14(e0214847)2019.PubMed/NCBI View Article : Google Scholar
8	Yeo CQX, Alexander I, Lin Z, Lim S, Aning OA, Kumar R, Sangthongpitag K, Pendharkar V, Ho VHB and Cheok CF: p53 maintains genomic stability by preventing interference between transcription and replication. Cell Rep. 15:132–146. 2016.PubMed/NCBI View Article : Google Scholar
9	Hirasawa H, Tanaka S, Sakai A, Tsutsui M, Shimokawa H, Miyata H, Moriwaki S, Niida S, Ito M and Nakamura T: ApoE gene deficiency enhances the reduction of bone formation induced by a high-fat diet through the stimulation of p53-mediated apoptosis in osteoblastic cells. J Bone Miner Res. 22:1020–1030. 2007.PubMed/NCBI View Article : Google Scholar
10	Weinstein RS and Manolagas SC: Apoptosis and osteoporosis. Am J Med. 108:153–164. 2000.PubMed/NCBI View Article : Google Scholar
11	Zhen YF, Wang GD, Zhu LQ, Tan SP, Zhang FY, Zhou XZ and Wang XD: P53 dependent mitochondrial permeability transition pore opening is required for dexamethasone-induced death of osteoblasts. J Cell Physiol. 229:1475–1483. 2014.PubMed/NCBI View Article : Google Scholar
12	Hao L, Fu J, Tian Y and Wu J: Systematic analysis of lncRNAs, miRNAs and mRNAs for the identification of biomarkers for osteoporosis in the mandible of ovariectomized mice. Int J Mol Med. 40:689–702. 2017.PubMed/NCBI View Article : Google Scholar
13	Cui L, Nai M, Zhang K, Li L and Li R: lncRNA WT1-AS inhibits the aggressiveness of cervical cancer cell via regulating p53 expression via sponging miR-330-5p. Cancer Manag Res. 11:651–667. 2019.PubMed/NCBI View Article : Google Scholar
14	Coulson KA, Reed G, Gilliam BE, Kremer JM and Pepmueller PH: Factors influencing fracture risk, T score, and management of osteoporosis in patients with rheumatoid arthritis in the Consortium of Rheumatology Researchers of North America (CORRONA) registry. J Clin Rheumatol. 15:155–160. 2009.PubMed/NCBI View Article : Google Scholar
15	Al-Azzawi F: Prevention of postmenopausal osteoporosis and associated fractures: Clinical evaluation of the choice between estrogen and bisphosphonates. Gynecol Endocrinol. 24:601–609. 2008.PubMed/NCBI View Article : Google Scholar
16	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.PubMed/NCBI View Article : Google Scholar
17	Du T, Zhang B, Zhang S, Jiang X, Zheng P, Li J, Yan M, Zhu Z and Liu B: Decreased expression of long non-coding RNA WT1-AS promotes cell proliferation and invasion in gastric cancer. Biochim Biophys Acta. 1862:12–19. 2016.PubMed/NCBI View Article : Google Scholar
18	Dai SG, Guo LL, Xia X and Pan Y: Long non-coding RNA WT1-AS inhibits cell aggressiveness via miR-203a-5p/FOXN2 axis and is associated with prognosis in cervical cancer. Eur Rev Med Pharmacol Sci. 23:486–495. 2019.PubMed/NCBI View Article : Google Scholar
19	Komori T: Cell death in chondrocytes, osteoblasts, and osteocytes. Int J Mol Sci. 17(2045)2016.PubMed/NCBI View Article : Google Scholar
20	Lorentzon M and Cummings SR: Osteoporosis: The evolution of a diagnosis. J Intern Med. 277:650–661. 2015.PubMed/NCBI View Article : Google Scholar
21	Thomson DW and Dinger ME: Endogenous microRNA sponges: Evidence and controversy. Nat Rev Genet. 17:272–283. 2016.PubMed/NCBI View Article : Google Scholar
22	Yu Y, Newman H, Shen L, Sharma D, Hu G, Mirando AJ, Zhang H, Knudsen E, Zhang GF, Hilton MJ, et al: Glutamine metabolism regulates proliferation and lineage allocation in skeletal stem cells. Cell Metab. 29:966–978. e4. 2019.PubMed/NCBI View Article : Google Scholar
23	Hayashi M, Nakashima T, Yoshimura N, Okamoto K, Tanaka S and Takayanagi H: Autoregulation of osteocyte Sema3A orchestrates estrogen action and counteracts bone aging. Cell Metab. 29:627–637.e5. 2019.PubMed/NCBI View Article : Google Scholar
24	Fan Y, Hanai JI, Le PT, Bi R, Maridas D, DeMambro V, Figueroa CA, Kir S, Zhou X, Mannstadt M, et al: Parathyroid hormone directs bone marrow mesenchymal cell fate. Cell Metab. 25:661–672. 2017.PubMed/NCBI View Article : Google Scholar
25	Stegen S, van Gastel N, Eelen G, Ghesquière B, D'Anna F, Thienpont B, Goveia J, Torrekens S, Van Looveren R, Luyten FP, et al: HIF-1α promotes glutamine-mediated redox homeostasis and glycogen-dependent bioenergetics to support postimplantation bone cell survival. Cell Metab. 23:265–279. 2016.PubMed/NCBI View Article : Google Scholar
26	Liu S, Liu D, Chen C, Hamamura K, Moshaverinia A, Yang R, Liu Y, Jin Y and Shi S: MSC transplantation improves osteopenia via epigenetic regulation of notch signaling in lupus. Cell Metab. 22:606–618. 2015.PubMed/NCBI View Article : Google Scholar
27	Mera P, Laue K, Ferron M, Confavreux C, Wei J, Galán-Díez M, Lacampagne A, Mitchell SJ, Mattison JA, Chen Y, et al: Osteocalcin signaling in myofibers is necessary and sufficient for optimum adaptation to exercise. Cell Metab. 23:1078–1092. 2016.PubMed/NCBI View Article : Google Scholar