Long Non-coding RNA SNHG12, a New Therapeutic Target, Regulates miR-199a-5p/Klotho to Promote the Growth and Metastasis of Intrahepatic Cholangiocarcinoma Cells
Background: Small nucleolar RNA host gene 12 (SNHG12) is a newly identified long non-coding RNA (lncRNA) whose involvements have been explored in several cancers. Our study aimed to explore the functions of SNHG12 on intrahepatic cholangiocarcinoma (ICC) progression and its interaction with miR-199a...
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2021.680378/full |
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| author | Hong-Guo Yang Hong-Guo Yang Tian-peng Wang Sheng-an Hu Chao-zhou Hu Cheng-hang Jiang Qiang He |
| author_facet | Hong-Guo Yang Hong-Guo Yang Tian-peng Wang Sheng-an Hu Chao-zhou Hu Cheng-hang Jiang Qiang He |
| author_sort | Hong-Guo Yang |
| collection | DOAJ |
| description | Background: Small nucleolar RNA host gene 12 (SNHG12) is a newly identified long non-coding RNA (lncRNA) whose involvements have been explored in several cancers. Our study aimed to explore the functions of SNHG12 on intrahepatic cholangiocarcinoma (ICC) progression and its interaction with miR-199a-5p and Klotho.Methods: RT-PCR was performed to examine the expressions of SNHG12, miR-199a-5p and Klotho in ICC cells. Cell counting kit-8 (CCK-8), colony formation assays and transwell assays were applied to analyze the proliferation, migration and invasion of ICC cells. Luciferase assays, RIP assays and RNA pull-down assays were carried out to demonstrate the direct binding relationships among SNHG12, miR-199a-5p and Klotho. The xenograft nude models were applied to test the effects of SNHG12 on ICC tumor growth.Results: The expression of SNHG12 and Klotho was distinctly increased in ICC cells, while miR-199a-5p expressions were decreased. Functionally, the silence of SNHG12 inhibited the proliferation and metastasis of ICC cells, while miR-199a-5p overexpression exhibited an opposite result. Mechanistically, Knockdown of SNHG12 significantly suppressed the expressions of miR-199a-5p by sponging it, and then increased Klotho expression. The final in vivo experiments suggested that the silence of SNHG12 distinctly inhibited tumor growth.Conclusion: Our findings indicated that SNHG12 inhibited cell proliferation and metastasis process of ICC cells through modulating the miR-199a-5p/Klotho axis and it is expected to become a potential therapeutic target for ICC. |
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| language | English |
| last_indexed | 2024-12-16T12:22:59Z |
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| spelling | doaj.art-f017671ead0d4536ae62e420b87a2e552022-12-21T22:31:54ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2021-06-01810.3389/fmed.2021.680378680378Long Non-coding RNA SNHG12, a New Therapeutic Target, Regulates miR-199a-5p/Klotho to Promote the Growth and Metastasis of Intrahepatic Cholangiocarcinoma CellsHong-Guo Yang0Hong-Guo Yang1Tian-peng Wang2Sheng-an Hu3Chao-zhou Hu4Cheng-hang Jiang5Qiang He6Department of Hepatobiliary & Pancreatic Surgery, Tongde Hospital of Zhejiang Province, Hangzhou, ChinaDepartment of Emergency, Zhejiang Provincial People's Hospital, Hangzhou, ChinaDepartment of Emergency, Zhejiang Provincial People's Hospital, Hangzhou, ChinaDepartment of Emergency, Zhejiang Provincial People's Hospital, Hangzhou, ChinaDepartment of Emergency, Zhejiang Provincial People's Hospital, Hangzhou, ChinaDepartment of Emergency, Zhejiang Provincial People's Hospital, Hangzhou, ChinaDepartment of General Surgery, Zhejiang Provincial People's Hospital, Haining Hospital, Haining, ChinaBackground: Small nucleolar RNA host gene 12 (SNHG12) is a newly identified long non-coding RNA (lncRNA) whose involvements have been explored in several cancers. Our study aimed to explore the functions of SNHG12 on intrahepatic cholangiocarcinoma (ICC) progression and its interaction with miR-199a-5p and Klotho.Methods: RT-PCR was performed to examine the expressions of SNHG12, miR-199a-5p and Klotho in ICC cells. Cell counting kit-8 (CCK-8), colony formation assays and transwell assays were applied to analyze the proliferation, migration and invasion of ICC cells. Luciferase assays, RIP assays and RNA pull-down assays were carried out to demonstrate the direct binding relationships among SNHG12, miR-199a-5p and Klotho. The xenograft nude models were applied to test the effects of SNHG12 on ICC tumor growth.Results: The expression of SNHG12 and Klotho was distinctly increased in ICC cells, while miR-199a-5p expressions were decreased. Functionally, the silence of SNHG12 inhibited the proliferation and metastasis of ICC cells, while miR-199a-5p overexpression exhibited an opposite result. Mechanistically, Knockdown of SNHG12 significantly suppressed the expressions of miR-199a-5p by sponging it, and then increased Klotho expression. The final in vivo experiments suggested that the silence of SNHG12 distinctly inhibited tumor growth.Conclusion: Our findings indicated that SNHG12 inhibited cell proliferation and metastasis process of ICC cells through modulating the miR-199a-5p/Klotho axis and it is expected to become a potential therapeutic target for ICC.https://www.frontiersin.org/articles/10.3389/fmed.2021.680378/fulllncRNA SNHG12intrahepatic cholangiocarcinomamiR-199a-5pKlothometastasis |
| spellingShingle | Hong-Guo Yang Hong-Guo Yang Tian-peng Wang Sheng-an Hu Chao-zhou Hu Cheng-hang Jiang Qiang He Long Non-coding RNA SNHG12, a New Therapeutic Target, Regulates miR-199a-5p/Klotho to Promote the Growth and Metastasis of Intrahepatic Cholangiocarcinoma Cells Frontiers in Medicine lncRNA SNHG12 intrahepatic cholangiocarcinoma miR-199a-5p Klotho metastasis |
| title | Long Non-coding RNA SNHG12, a New Therapeutic Target, Regulates miR-199a-5p/Klotho to Promote the Growth and Metastasis of Intrahepatic Cholangiocarcinoma Cells |
| title_full | Long Non-coding RNA SNHG12, a New Therapeutic Target, Regulates miR-199a-5p/Klotho to Promote the Growth and Metastasis of Intrahepatic Cholangiocarcinoma Cells |
| title_fullStr | Long Non-coding RNA SNHG12, a New Therapeutic Target, Regulates miR-199a-5p/Klotho to Promote the Growth and Metastasis of Intrahepatic Cholangiocarcinoma Cells |
| title_full_unstemmed | Long Non-coding RNA SNHG12, a New Therapeutic Target, Regulates miR-199a-5p/Klotho to Promote the Growth and Metastasis of Intrahepatic Cholangiocarcinoma Cells |
| title_short | Long Non-coding RNA SNHG12, a New Therapeutic Target, Regulates miR-199a-5p/Klotho to Promote the Growth and Metastasis of Intrahepatic Cholangiocarcinoma Cells |
| title_sort | long non coding rna snhg12 a new therapeutic target regulates mir 199a 5p klotho to promote the growth and metastasis of intrahepatic cholangiocarcinoma cells |
| topic | lncRNA SNHG12 intrahepatic cholangiocarcinoma miR-199a-5p Klotho metastasis |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2021.680378/full |
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