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Published in: Inflammation 3/2018

01-06-2018 | ORIGINAL ARTICLE

The lncRNA H19 Mediates Pulmonary Fibrosis by Regulating the miR-196a/COL1A1 Axis

Authors: Qingchun Lu, Zhongliang Guo, Wang Xie, Wenjing Jin, Dongyi Zhu, Song Chen, Tao Ren

Published in: Inflammation | Issue 3/2018

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Abstract

Idiopathic pulmonary fibrosis (IPF) is characterized by lung fibroblasts accumulation and extracellular matrix (ECM) deposition. Recently, long-noncoding RNAs (lncRNAs) have emerged as critical regulators and prognostic markers in several diseases including IPF. In the present study, we found that the expression of H19 was significantly increased in transforming growth factor-β (TGF-β)-induced fibroblast proliferation and bleomycin-(BLM) induced lung fibrosis (p < 0.05). We further demonstrated that H19 was a direct target of miR-196a and was associated with COL1A1 expression by sponging miR-196a. Moreover, downregulation of H19 alleviated fibroblast activation and lung fibrosis, and this effect was blocked by a miR-196a inhibitor. In conclusion, our results suggest that lncRNA H19 has a promotive effect on BLM-induced IPF, and it functions as a molecular sponge of miR-196a, which provides a novel therapeutic target for IPF.
Literature
1.
go back to reference King, T.E., Jr., A. Pardo, and M. Selman. 2011. Idiopathic pulmonary fibrosis. Lancet 378 (9807): 1949–1961.CrossRefPubMed King, T.E., Jr., A. Pardo, and M. Selman. 2011. Idiopathic pulmonary fibrosis. Lancet 378 (9807): 1949–1961.CrossRefPubMed
2.
go back to reference Lee, Y.J., M.J. Kim, Y.S. Yoon, Y.H. Choi, H.S. Kim, and J.L. Kang. 2017. Simvastatin treatment boosts benefits of apoptotic cell infusion in murine lung fibrosis. Cell Death & Disease 8 (6): e2860.CrossRef Lee, Y.J., M.J. Kim, Y.S. Yoon, Y.H. Choi, H.S. Kim, and J.L. Kang. 2017. Simvastatin treatment boosts benefits of apoptotic cell infusion in murine lung fibrosis. Cell Death & Disease 8 (6): e2860.CrossRef
3.
go back to reference Wu, D.D., X. Chen, K.X. Sun, L.L. Wang, S. Chen, and Y. Zhao. 2017. Role of the lncRNA ABHD11-AS1 in the tumorigenesis and progression of epithelial ovarian cancer through targeted regulation of RhoC. Molecular Cancer 16 (1): 138.CrossRefPubMedPubMedCentral Wu, D.D., X. Chen, K.X. Sun, L.L. Wang, S. Chen, and Y. Zhao. 2017. Role of the lncRNA ABHD11-AS1 in the tumorigenesis and progression of epithelial ovarian cancer through targeted regulation of RhoC. Molecular Cancer 16 (1): 138.CrossRefPubMedPubMedCentral
4.
go back to reference Xie, H., J.D. Xue, F. Chao, Y.F. Jin, and Q. Fu. 2016. Long non-coding RNA-H19 antagonism protects against renal fibrosis. Oncotarget 7 (32): 51473–51481.PubMedPubMedCentral Xie, H., J.D. Xue, F. Chao, Y.F. Jin, and Q. Fu. 2016. Long non-coding RNA-H19 antagonism protects against renal fibrosis. Oncotarget 7 (32): 51473–51481.PubMedPubMedCentral
5.
go back to reference Qu, X., X. Song, W. Yuan, Y. Shu, Y. Wang, X. Zhao, M. Gao, R. Lu, S. Luo, W. Zhao, Y. Zhang, L. Sun, and Y. Lu. 2016. Expression signature of lncRNAs and their potential roles in cardiac fibrosis of post-infarct mice. Bioscience Reports 36 (3): e00337. Qu, X., X. Song, W. Yuan, Y. Shu, Y. Wang, X. Zhao, M. Gao, R. Lu, S. Luo, W. Zhao, Y. Zhang, L. Sun, and Y. Lu. 2016. Expression signature of lncRNAs and their potential roles in cardiac fibrosis of post-infarct mice. Bioscience Reports 36 (3): e00337.
6.
go back to reference Huang, C., Y. Yang, and L. Liu. 2015. Interaction of long noncoding RNAs and microRNAs in the pathogenesis of idiopathic pulmonary fibrosis. Physiological Genomics 47 (10): 463–469.CrossRefPubMedPubMedCentral Huang, C., Y. Yang, and L. Liu. 2015. Interaction of long noncoding RNAs and microRNAs in the pathogenesis of idiopathic pulmonary fibrosis. Physiological Genomics 47 (10): 463–469.CrossRefPubMedPubMedCentral
7.
go back to reference Raveh, E., I.J. Matouk, M. Gilon, and A. Hochberg. 2015. The H19 long non-coding RNA in cancer initiation, progression and metastasis - a proposed unifying theory. Molecular Cancer 14: 184.CrossRefPubMedPubMedCentral Raveh, E., I.J. Matouk, M. Gilon, and A. Hochberg. 2015. The H19 long non-coding RNA in cancer initiation, progression and metastasis - a proposed unifying theory. Molecular Cancer 14: 184.CrossRefPubMedPubMedCentral
8.
go back to reference Tang, Y., R. He, J. An, P. Deng, L. Huang, and W. Yang. 2016. The effect of H19-miR-29b interaction on bleomycin-induced mouse model of idiopathic pulmonary fibrosis. Biochemical and Biophysical Research Communications 479 (3): 417–423.CrossRefPubMed Tang, Y., R. He, J. An, P. Deng, L. Huang, and W. Yang. 2016. The effect of H19-miR-29b interaction on bleomycin-induced mouse model of idiopathic pulmonary fibrosis. Biochemical and Biophysical Research Communications 479 (3): 417–423.CrossRefPubMed
9.
go back to reference Tong, H.L., R.Y. Jiang, W.W. Zhang, and Y.Q. Yan. 2017. MiR-2425-5p targets RAD9A and MYOG to regulate the proliferation and differentiation of bovine skeletal muscle-derived satellite cells. Scientific Reports 7 (1): 418.CrossRefPubMedPubMedCentral Tong, H.L., R.Y. Jiang, W.W. Zhang, and Y.Q. Yan. 2017. MiR-2425-5p targets RAD9A and MYOG to regulate the proliferation and differentiation of bovine skeletal muscle-derived satellite cells. Scientific Reports 7 (1): 418.CrossRefPubMedPubMedCentral
10.
go back to reference Mizuno, K., H. Mataki, N. Seki, T. Kumamoto, K. Kamikawaji, and H. Inoue. 2017. MicroRNAs in non-small cell lung cancer and idiopathic pulmonary fibrosis. Journal of Human Genetics 62 (1): 57–65.CrossRefPubMed Mizuno, K., H. Mataki, N. Seki, T. Kumamoto, K. Kamikawaji, and H. Inoue. 2017. MicroRNAs in non-small cell lung cancer and idiopathic pulmonary fibrosis. Journal of Human Genetics 62 (1): 57–65.CrossRefPubMed
11.
go back to reference Ji, X., B. Wu, J. Fan, R. Han, C. Luo, T. Wang, J. Yang, L. Han, B. Zhu, D. Wei, J. Chen, and C. Ni. 2015. The anti-fibrotic effects and mechanisms of microRNA-486-5p in pulmonary fibrosis. Scientific Reports 5: 14131.CrossRefPubMedPubMedCentral Ji, X., B. Wu, J. Fan, R. Han, C. Luo, T. Wang, J. Yang, L. Han, B. Zhu, D. Wei, J. Chen, and C. Ni. 2015. The anti-fibrotic effects and mechanisms of microRNA-486-5p in pulmonary fibrosis. Scientific Reports 5: 14131.CrossRefPubMedPubMedCentral
12.
go back to reference Wu, Q., L. Han, W. Yan, X. Ji, R. Han, J. Yang, J. Yuan, and C. Ni. 2016. miR-489 inhibits silica-induced pulmonary fibrosis by targeting MyD88 and Smad3 and is negatively regulated by lncRNA CHRF. Scientific Reports 6 (30921). Wu, Q., L. Han, W. Yan, X. Ji, R. Han, J. Yang, J. Yuan, and C. Ni. 2016. miR-489 inhibits silica-induced pulmonary fibrosis by targeting MyD88 and Smad3 and is negatively regulated by lncRNA CHRF. Scientific Reports 6 (30921).
13.
go back to reference Jin, C., Y. Zhang, and J. Li. 2016. Upregulation of MiR-196a promotes cell proliferation by downregulating p27kip1 in laryngeal cancer. Biological Research 49 (1): 40.CrossRefPubMedPubMedCentral Jin, C., Y. Zhang, and J. Li. 2016. Upregulation of MiR-196a promotes cell proliferation by downregulating p27kip1 in laryngeal cancer. Biological Research 49 (1): 40.CrossRefPubMedPubMedCentral
14.
go back to reference Ma, Y., B. Wang, Y. Guo, Y. Zhang, S. Huang, X. Bao, and M. Bai. 2016. Inhibition of miR-196a affects esophageal cancer cell growth in vitro. Biomedicine & Pharmacotherapy 84: 22–27.CrossRef Ma, Y., B. Wang, Y. Guo, Y. Zhang, S. Huang, X. Bao, and M. Bai. 2016. Inhibition of miR-196a affects esophageal cancer cell growth in vitro. Biomedicine & Pharmacotherapy 84: 22–27.CrossRef
15.
go back to reference Meng, J., L. Li, Y. Zhao, Z. Zhou, M. Zhang, D. Li, C.Y. Zhang, K. Zen, and Z. Liu. 2016. MicroRNA-196a/b mitigate renal fibrosis by targeting TGF-beta receptor 2. Journal of the American Society of Nephrology 27 (10): 3006–3021.CrossRefPubMedPubMedCentral Meng, J., L. Li, Y. Zhao, Z. Zhou, M. Zhang, D. Li, C.Y. Zhang, K. Zen, and Z. Liu. 2016. MicroRNA-196a/b mitigate renal fibrosis by targeting TGF-beta receptor 2. Journal of the American Society of Nephrology 27 (10): 3006–3021.CrossRefPubMedPubMedCentral
16.
go back to reference Kashiyama, K., N. Mitsutake, M. Matsuse, T. Ogi, V.A. Saenko, K. Ujifuku, A. Utani, A. Hirano, and S. Yamashita. 2012. miR-196a downregulation increases the expression of type I and III collagens in keloid fibroblasts. The Journal of Investigative Dermatology 132 (6): 1597–1604.CrossRefPubMed Kashiyama, K., N. Mitsutake, M. Matsuse, T. Ogi, V.A. Saenko, K. Ujifuku, A. Utani, A. Hirano, and S. Yamashita. 2012. miR-196a downregulation increases the expression of type I and III collagens in keloid fibroblasts. The Journal of Investigative Dermatology 132 (6): 1597–1604.CrossRefPubMed
21.
go back to reference Wang, S.H., F. Ma, Z.H. Tang, X.C. Wu, Q. Cai, M.D. Zhang, M.Z. Weng, D. Zhou, J.D. Wang, and Z.W. Quan. 2016. Long non-coding RNA H19 regulates FOXM1 expression by competitively binding endogenous miR-342-3p in gallbladder cancer. Journal of Experimental & Clinical Cancer Research 35 (1): 160.CrossRef Wang, S.H., F. Ma, Z.H. Tang, X.C. Wu, Q. Cai, M.D. Zhang, M.Z. Weng, D. Zhou, J.D. Wang, and Z.W. Quan. 2016. Long non-coding RNA H19 regulates FOXM1 expression by competitively binding endogenous miR-342-3p in gallbladder cancer. Journal of Experimental & Clinical Cancer Research 35 (1): 160.CrossRef
22.
go back to reference Su, Z., X. Zhi, Q. Zhang, L. Yang, H. Xu, and Z. Xu. 2016. LncRNA H19 functions as a competing endogenous RNA to regulate AQP3 expression by sponging miR-874 in the intestinal barrier. FEBS Letters 590 (9): 1354–1364.CrossRefPubMed Su, Z., X. Zhi, Q. Zhang, L. Yang, H. Xu, and Z. Xu. 2016. LncRNA H19 functions as a competing endogenous RNA to regulate AQP3 expression by sponging miR-874 in the intestinal barrier. FEBS Letters 590 (9): 1354–1364.CrossRefPubMed
23.
go back to reference Shen, L., G. Zhang, Z. Lou, and G. Xu. 2017. Cryptotanshinone enhances the effect of arsenic trioxide in treating liver cancer cell by inducing apoptosis through downregulating phosphorylated- STAT3 in vitro and in vivo. BMC Complementary and Alternative Medicine 17 (1): 106.CrossRefPubMedPubMedCentral Shen, L., G. Zhang, Z. Lou, and G. Xu. 2017. Cryptotanshinone enhances the effect of arsenic trioxide in treating liver cancer cell by inducing apoptosis through downregulating phosphorylated- STAT3 in vitro and in vivo. BMC Complementary and Alternative Medicine 17 (1): 106.CrossRefPubMedPubMedCentral
24.
go back to reference Sun, H., J. Chen, W. Qian, J. Kang, J. Wang, L. Jiang, L. Qiao, W. Chen, and J. Zhang. 2016. Integrated long non-coding RNA analyses identify novel regulators of epithelial-mesenchymal transition in the mouse model of pulmonary fibrosis. Journal of Cellular and Molecular Medicine 20 (7): 1234–1246.CrossRefPubMedPubMedCentral Sun, H., J. Chen, W. Qian, J. Kang, J. Wang, L. Jiang, L. Qiao, W. Chen, and J. Zhang. 2016. Integrated long non-coding RNA analyses identify novel regulators of epithelial-mesenchymal transition in the mouse model of pulmonary fibrosis. Journal of Cellular and Molecular Medicine 20 (7): 1234–1246.CrossRefPubMedPubMedCentral
25.
go back to reference Salmena, L., L. Poliseno, Y. Tay, L. Kats, and P.P. Pandolfi. 2011. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell 146 (3): 353–358.CrossRefPubMedPubMedCentral Salmena, L., L. Poliseno, Y. Tay, L. Kats, and P.P. Pandolfi. 2011. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell 146 (3): 353–358.CrossRefPubMedPubMedCentral
27.
go back to reference Burgess, J.K., T. Mauad, G. Tjin, J.C. Karlsson, and G. Westergren-Thorsson. 2016. The extracellular matrix—the under-recognized element in lung disease? The Journal of Pathology 240 (4): 397–409.CrossRefPubMedPubMedCentral Burgess, J.K., T. Mauad, G. Tjin, J.C. Karlsson, and G. Westergren-Thorsson. 2016. The extracellular matrix—the under-recognized element in lung disease? The Journal of Pathology 240 (4): 397–409.CrossRefPubMedPubMedCentral
Metadata
Title
The lncRNA H19 Mediates Pulmonary Fibrosis by Regulating the miR-196a/COL1A1 Axis
Authors
Qingchun Lu
Zhongliang Guo
Wang Xie
Wenjing Jin
Dongyi Zhu
Song Chen
Tao Ren
Publication date
01-06-2018
Publisher
Springer US
Published in
Inflammation / Issue 3/2018
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-018-0744-4

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