CDKN2B antisense RNA 1 expression alleviates idiopathic pulmonary fibrosis by functioning as a competing endogenouse RNA through the miR-199a-5p/Sestrin-2 axis

被引:15
作者
Yang, Mei [1 ,2 ]
Yin, Egao [1 ]
Xu, Yiheng [3 ]
Liu, Yongjun [1 ]
Li, Ting [4 ,5 ]
Dong, Zhaoxing [4 ,5 ]
Tai, Wenlin [3 ]
机构
[1] Kunming Med Univ, Dept Respirat, Affiliated Hosp 2, Kunming, Yunnan, Peoples R China
[2] Yunnan Univ, Dept Resp & Crit Care, Affiliated Hosp, Kunming, Yunnan, Peoples R China
[3] Kunming Med Univ, Yunnan Mol Diagnost Ctr, Dept Clin Lab, Affiliated Hosp 2, Kunming, Yunnan, Peoples R China
[4] Univ Chinese Acad Sci, Hwa Mei Hosp, Dept Respirat, Ningbo, Zhejiang, Peoples R China
[5] Univ Chinese Acad Sci, Ningbo Inst Life & Hlth Ind, Dept Respirat, Ningbo, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
CDKN2B-AS1; IPF; miR-199a-5p; SESN2; autophagy; LONG NONCODING RNA; AUTOPHAGY; LNCRNAS; PATHOGENESIS;
D O I
10.1080/21655979.2022.2044252
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Idiopathic pulmonary fibrosis (IPF) is an idiopathic interstitial lung disease. At present, the pathogenesis of IPF has not been fully elucidated, which has affected the development of effective treatment methods. Here, we explored the function and potential mechanism of long noncoding RNA (lncRNA) CDKN2B antisense RNA 1 (CDKN2B-AS1) in IPF.Transforming growth factor-beta (TGF-beta) and bleomycin (BLM) were used to induce IPF in cells and animal models. Real Time quantitative Polymerase Chain Reaction (RT-qPCR) showed the expression of CDKN2B-AS1, miR-199a-5p and Sestrin-2 (SESN2) in cells and tissues. The double luciferase reporter gene assay confirmed the targeting relationship among CDKN2B-AS1, miR-199a-5p, and SESN2. Related protein levels were detected by Western blot combined with Cell Counting Kit-8 (CCK-8), wound healing, and flow cytometry to analyze cell proliferation, migration, and apoptosis. The pathological characteristics of mouse lung tissue were determined by Hematoxylin-eosin (HE) and Masson staining. We found that the expression of CDKN2B-AS1 was decreased in TGF-beta-treated cells and BLM-treated mice. Overexpression of CDKN2B-AS1 inhibited cell proliferation and migration, promoted apoptosis, decreased the expression of fibrosis-related proteins and promoted autophagy. In addition, overexpression of CDKN2B-AS1 alleviated pulmonary fibrosis in BLM-treated mice. Mechanistically, CDKN2B-AS1 acts as a miR-199a-5p sponge to regulate SESN2 expression. Our results indicate the importance of the CDKN2B-AS1/miR-199a-5p/SESN2 axis.
引用
收藏
页码:7746 / 7759
页数:14
相关论文
共 38 条
[1]   Lysine-specific demethylase LSD1 regulates autophagy in neuroblastoma through SESN2-dependent pathway [J].
Ambrosio, S. ;
Sacca, C. D. ;
Amente, S. ;
Paladino, S. ;
Lania, L. ;
Majello, B. .
ONCOGENE, 2017, 36 (48) :6701-6711
[2]   Decoding Crucial LncRNAs Implicated in Neurogenesis and Neurological Disorders [J].
Ayana, R. ;
Singh, Shailja ;
Pati, Soumya .
STEM CELLS AND DEVELOPMENT, 2017, 26 (08) :541-553
[3]   LncRNA AIRN influences the proliferation and apoptosis of hepatocellular carcinoma cells by regulating STAT1 ubiquitination [J].
Cai, Huajie ;
Zheng, Yihu ;
Wen, Zhengde ;
Yang, Yingnan ;
Yang, Shouzhang ;
Zhang, Qiyu .
ARCHIVES OF PHARMACAL RESEARCH, 2021, 44 (04) :414-426
[4]   miR-199a-5p Is Upregulated during Fibrogenic Response to Tissue Injury and Mediates TGFbeta-Induced Lung Fibroblast Activation by Targeting Caveolin-1 [J].
Cardenas, Christian Lacks Lino ;
Henaoui, Imene Sarah ;
Courcot, Elisabeth ;
Roderburg, Christoph ;
Cauffiez, Christelle ;
Aubert, Sebastien ;
Copin, Marie-Christine ;
Wallaert, Benoit ;
Glowacki, Francois ;
Dewaeles, Edmone ;
Milosevic, Jadranka ;
Maurizio, Julien ;
Tedrow, John ;
Marcet, Brice ;
Lo-Guidice, Jean-Marc ;
Kaminski, Naftali ;
Barbry, Pascal ;
Luedde, Tom ;
Perrais, Michael ;
Mari, Bernard ;
Pottier, Nicolas .
PLOS GENETICS, 2013, 9 (02)
[5]   Overexpression of CDKN2B is involved in poor gastric cancer prognosis [J].
Chen, Xi ;
Yu, Xingtong ;
Shen, Enjian .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2019, 120 (12) :19825-19831
[6]   Mangiferin inhibits apoptosis and oxidative stress via BMP2/Smad-1 signaling in dexamethasone-induced MC3T3-E1 cells [J].
Ding, Ling-Zhi ;
Teng, Xiao ;
Zhang, Zhao-Bo ;
Zheng, Chang-Jun ;
Chen, Shi-Hong .
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2018, 41 (05) :2517-2526
[7]   Low expression of long noncoding RNA CDKN2B-AS1 in patients with idiopathic pulmonary fibrosis predicts lung cancer by regulating the p53-signaling pathway [J].
Du, Yufeng ;
Hao, Xiaoyan ;
Liu, Xuejun .
ONCOLOGY LETTERS, 2018, 15 (04) :4912-4918
[8]   COTI-2 induces cell apoptosis in pediatric acute lymphoblastic leukemia via upregulation of miR-203 [J].
Guo, Yingmeng ;
Zhua, Xia ;
Sun, Xuerong .
BIOENGINEERED, 2020, 11 (01) :201-208
[9]   Inflammation and immunity in IPF pathogenesis and treatment [J].
Heukels, P. ;
Moor, C. C. ;
von der Thusen, J. H. ;
Wijsenbeek, M. S. ;
Kool, M. .
RESPIRATORY MEDICINE, 2019, 147 :79-91
[10]   Autophagy inhibition-mediated epithelial-mesenchymal transition augments local myofibroblast differentiation in pulmonary fibrosis [J].
Hill, Charlotte ;
Li, Juanjuan ;
Liu, Dian ;
Conforti, Franco ;
Brereton, Christopher J. ;
Yao, Liudi ;
Zhou, Yilu ;
Alzetani, Aiman ;
Chee, Serena J. ;
Marshall, Ben G. ;
Fletcher, Sophie V. ;
Hancock, David ;
Ottensmeier, Christian H. ;
Steele, Andrew J. ;
Downward, Julian ;
Richeldi, Luca ;
Lu, Xin ;
Davies, Donna E. ;
Jones, Mark G. ;
Wang, Yihua .
CELL DEATH & DISEASE, 2019, 10 (8)