Long Noncoding RNA HOTTIP Promotes Mouse Hepatic Stellate Cell Activation via Downregulating miR-148a
Background/Aims: HOTTIP is a critical modulator in human diseases including liver cancer, but its role and molecular biological mechanisms in liver fibrosis are still unclear. Methods: The expression profile of HOTTIP during the progression of liver fibrosis was detected in human liver samples and i...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2018-12-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | https://www.karger.com/Article/FullText/496012 |
| _version_ | 1811281802342432768 |
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| author | Zhiqin Li Jia Wang Qinglei Zeng Chunling Hu Jiajia Zhang Hongyan Wang Jingya Yan Hua Li Zujiang Yu |
| author_facet | Zhiqin Li Jia Wang Qinglei Zeng Chunling Hu Jiajia Zhang Hongyan Wang Jingya Yan Hua Li Zujiang Yu |
| author_sort | Zhiqin Li |
| collection | DOAJ |
| description | Background/Aims: HOTTIP is a critical modulator in human diseases including liver cancer, but its role and molecular biological mechanisms in liver fibrosis are still unclear. Methods: The expression profile of HOTTIP during the progression of liver fibrosis was detected in human liver samples and in CCl4-treated mice using qRT-PCR. The expressing sh-HOTTIP adenoviral vector was used to reduce HOTTIP levels in vivo. Dual-Luciferase Reporter Assay was performed to validate the interaction between miR-148a and HOTTIP, TGFBR1, or TGFBR2. Results: HOTTIP expressions in fibrotic liver samples and cirrhotic liver samples were significantly upregulated compared with healthy liver controls, and cirrhotic samples exhibited the highest levels of HOTTIP. Moreover, HOTTIP expressions were substantially induced in the liver tissues and hepatic stellate cells (HSC) of CCl4-treated mice. Ad-shHOTTIP delivery could alleviate CCl4- induced liver fibrosis in mice. Down-regulation of HOTTIP inhibited the viability and activation of HSCs in vitro, and HOTTIP negatively regulated miR-148a expression in HSCs. miR-148a had a negative effect on HSC activation by targeting TGFBR1 and TGFBR2. Conclusion: HOTTIP is involved in the progression of liver fibrosis by promoting HSC activation. The high level of HOTTIP downregulates miR-148a, thus to increase the level of TGFBR1 and TGFBR2 and contribute to liver fibrosis. |
| first_indexed | 2024-04-13T01:40:09Z |
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| id | doaj.art-dc3b38b1b0544510b1c2a1e1358672c5 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-04-13T01:40:09Z |
| publishDate | 2018-12-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-dc3b38b1b0544510b1c2a1e1358672c52022-12-22T03:08:14ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-12-015162814282810.1159/000496012496012Long Noncoding RNA HOTTIP Promotes Mouse Hepatic Stellate Cell Activation via Downregulating miR-148aZhiqin LiJia WangQinglei ZengChunling HuJiajia ZhangHongyan WangJingya YanHua LiZujiang YuBackground/Aims: HOTTIP is a critical modulator in human diseases including liver cancer, but its role and molecular biological mechanisms in liver fibrosis are still unclear. Methods: The expression profile of HOTTIP during the progression of liver fibrosis was detected in human liver samples and in CCl4-treated mice using qRT-PCR. The expressing sh-HOTTIP adenoviral vector was used to reduce HOTTIP levels in vivo. Dual-Luciferase Reporter Assay was performed to validate the interaction between miR-148a and HOTTIP, TGFBR1, or TGFBR2. Results: HOTTIP expressions in fibrotic liver samples and cirrhotic liver samples were significantly upregulated compared with healthy liver controls, and cirrhotic samples exhibited the highest levels of HOTTIP. Moreover, HOTTIP expressions were substantially induced in the liver tissues and hepatic stellate cells (HSC) of CCl4-treated mice. Ad-shHOTTIP delivery could alleviate CCl4- induced liver fibrosis in mice. Down-regulation of HOTTIP inhibited the viability and activation of HSCs in vitro, and HOTTIP negatively regulated miR-148a expression in HSCs. miR-148a had a negative effect on HSC activation by targeting TGFBR1 and TGFBR2. Conclusion: HOTTIP is involved in the progression of liver fibrosis by promoting HSC activation. The high level of HOTTIP downregulates miR-148a, thus to increase the level of TGFBR1 and TGFBR2 and contribute to liver fibrosis.https://www.karger.com/Article/FullText/496012Liver fibrosisHSC activationHOTTIPmiR-148a |
| spellingShingle | Zhiqin Li Jia Wang Qinglei Zeng Chunling Hu Jiajia Zhang Hongyan Wang Jingya Yan Hua Li Zujiang Yu Long Noncoding RNA HOTTIP Promotes Mouse Hepatic Stellate Cell Activation via Downregulating miR-148a Cellular Physiology and Biochemistry Liver fibrosis HSC activation HOTTIP miR-148a |
| title | Long Noncoding RNA HOTTIP Promotes Mouse Hepatic Stellate Cell Activation via Downregulating miR-148a |
| title_full | Long Noncoding RNA HOTTIP Promotes Mouse Hepatic Stellate Cell Activation via Downregulating miR-148a |
| title_fullStr | Long Noncoding RNA HOTTIP Promotes Mouse Hepatic Stellate Cell Activation via Downregulating miR-148a |
| title_full_unstemmed | Long Noncoding RNA HOTTIP Promotes Mouse Hepatic Stellate Cell Activation via Downregulating miR-148a |
| title_short | Long Noncoding RNA HOTTIP Promotes Mouse Hepatic Stellate Cell Activation via Downregulating miR-148a |
| title_sort | long noncoding rna hottip promotes mouse hepatic stellate cell activation via downregulating mir 148a |
| topic | Liver fibrosis HSC activation HOTTIP miR-148a |
| url | https://www.karger.com/Article/FullText/496012 |
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