LncRNA SNHG8 upregulates MUC5B to induce idiopathic pulmonary fibrosis progression by targeting miR-4701-5p
Long noncoding RNAs (lncRNAs) play a critical role in idiopathic pulmonary fibrosis (IPF); however, the underlying molecular mechanisms are unclear. Our study demonstrated that lncRNA small nucleolar RNA host gene 8 (SNHG8) was increased in bleomycin (BLM)-induced A549 cells. LncRNA SNHG8 overexpres...
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| Format: | Article |
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Elsevier
2024-01-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023104415 |
| _version_ | 1797337117363273728 |
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| author | Xiaoping Zhang Runxia Shao |
| author_facet | Xiaoping Zhang Runxia Shao |
| author_sort | Xiaoping Zhang |
| collection | DOAJ |
| description | Long noncoding RNAs (lncRNAs) play a critical role in idiopathic pulmonary fibrosis (IPF); however, the underlying molecular mechanisms are unclear. Our study demonstrated that lncRNA small nucleolar RNA host gene 8 (SNHG8) was increased in bleomycin (BLM)-induced A549 cells. LncRNA SNHG8 overexpression further elevated fibrosis-related factors monocyte chemotactic protein 1 (MCP1), CC motif chemokine ligand 18 (CCL18), and α-smooth muscle actin (α-SMA), as well as increased collagen type I alpha-1 chain (COL1A1) and collagen type III alpha-1 chain (COL3A1). Meanwhile, lncRNA SNHG8 knockdown exhibited an opposite role in reducing BLM-induced pulmonary fibrosis. With regard to the mechanism, SNHG8 was then revealed to act as a competing endogenous RNA (ceRNA) for microRNA (miR)-4701-5p in regulating Mucin 5B (MUC5B) expression. Furthermore, the interactions between SNHG8 and miR-4701-5p, between miR-4701-5p and MUC5B, and between SNHG8 and MUC5B on the influence of fibrosis-related indicators were confirmed, respectively. In addition, SNHG8 overexpression enhanced the levels of transforming growth factor (TGF)-β1 and phosphorylation Smad2/3 (p-Smad2/3), which was suppressed by SNHG8 knockdown in BLM-induced A549 cells. Moreover, miR-4701-5p inhibitor-induced elevation of TGF-β1 and p-Smad2/3 was significantly suppressed by SNHG8 knockdown. In conclusion, SNHG8 knockdown attenuated pulmonary fibrosis progression by regulating miR-4701-5p/MUC5B axis, which might be associated with the modulation of TGF-β1/Smad2/3 signaling. These findings reveal that lncRNA SNHG8 may become a potential target for the treatment of IPF. |
| first_indexed | 2024-03-08T09:03:50Z |
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| language | English |
| last_indexed | 2024-03-08T09:03:50Z |
| publishDate | 2024-01-01 |
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| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-c095ee6ee40a4ea5b893894446e6afba2024-02-01T06:31:08ZengElsevierHeliyon2405-84402024-01-01101e23233LncRNA SNHG8 upregulates MUC5B to induce idiopathic pulmonary fibrosis progression by targeting miR-4701-5pXiaoping Zhang0Runxia Shao1Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, ChinaCorresponding author.; Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, ChinaLong noncoding RNAs (lncRNAs) play a critical role in idiopathic pulmonary fibrosis (IPF); however, the underlying molecular mechanisms are unclear. Our study demonstrated that lncRNA small nucleolar RNA host gene 8 (SNHG8) was increased in bleomycin (BLM)-induced A549 cells. LncRNA SNHG8 overexpression further elevated fibrosis-related factors monocyte chemotactic protein 1 (MCP1), CC motif chemokine ligand 18 (CCL18), and α-smooth muscle actin (α-SMA), as well as increased collagen type I alpha-1 chain (COL1A1) and collagen type III alpha-1 chain (COL3A1). Meanwhile, lncRNA SNHG8 knockdown exhibited an opposite role in reducing BLM-induced pulmonary fibrosis. With regard to the mechanism, SNHG8 was then revealed to act as a competing endogenous RNA (ceRNA) for microRNA (miR)-4701-5p in regulating Mucin 5B (MUC5B) expression. Furthermore, the interactions between SNHG8 and miR-4701-5p, between miR-4701-5p and MUC5B, and between SNHG8 and MUC5B on the influence of fibrosis-related indicators were confirmed, respectively. In addition, SNHG8 overexpression enhanced the levels of transforming growth factor (TGF)-β1 and phosphorylation Smad2/3 (p-Smad2/3), which was suppressed by SNHG8 knockdown in BLM-induced A549 cells. Moreover, miR-4701-5p inhibitor-induced elevation of TGF-β1 and p-Smad2/3 was significantly suppressed by SNHG8 knockdown. In conclusion, SNHG8 knockdown attenuated pulmonary fibrosis progression by regulating miR-4701-5p/MUC5B axis, which might be associated with the modulation of TGF-β1/Smad2/3 signaling. These findings reveal that lncRNA SNHG8 may become a potential target for the treatment of IPF.http://www.sciencedirect.com/science/article/pii/S2405844023104415IPFlncRNA SNHG8miR-4701-5pMUC5BTGF-β1/Smad2/3 signaling |
| spellingShingle | Xiaoping Zhang Runxia Shao LncRNA SNHG8 upregulates MUC5B to induce idiopathic pulmonary fibrosis progression by targeting miR-4701-5p Heliyon IPF lncRNA SNHG8 miR-4701-5p MUC5B TGF-β1/Smad2/3 signaling |
| title | LncRNA SNHG8 upregulates MUC5B to induce idiopathic pulmonary fibrosis progression by targeting miR-4701-5p |
| title_full | LncRNA SNHG8 upregulates MUC5B to induce idiopathic pulmonary fibrosis progression by targeting miR-4701-5p |
| title_fullStr | LncRNA SNHG8 upregulates MUC5B to induce idiopathic pulmonary fibrosis progression by targeting miR-4701-5p |
| title_full_unstemmed | LncRNA SNHG8 upregulates MUC5B to induce idiopathic pulmonary fibrosis progression by targeting miR-4701-5p |
| title_short | LncRNA SNHG8 upregulates MUC5B to induce idiopathic pulmonary fibrosis progression by targeting miR-4701-5p |
| title_sort | lncrna snhg8 upregulates muc5b to induce idiopathic pulmonary fibrosis progression by targeting mir 4701 5p |
| topic | IPF lncRNA SNHG8 miR-4701-5p MUC5B TGF-β1/Smad2/3 signaling |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023104415 |
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