Long Non-Coding RNA KCNQ1OT1 Promotes Cataractogenesis via miR-214 and Activation of the Caspase-1 Pathway
Background/Aims: KCNQ1OT1 regulates the expression of tissue-specific imprinted genes within the Kcnq1 domain. Imprinted genes are positive regulators of apoptosis, one of the forms of cell death related to cataract formation, and thus may provide novel therapeutic targets for cataract treatment. He...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2017-05-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | http://www.karger.com/Article/FullText/477330 |
| _version_ | 1818269147719532544 |
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| author | Xin Jin Hao Jin Yan Shi Yiyuan Guo Hong Zhang |
| author_facet | Xin Jin Hao Jin Yan Shi Yiyuan Guo Hong Zhang |
| author_sort | Xin Jin |
| collection | DOAJ |
| description | Background/Aims: KCNQ1OT1 regulates the expression of tissue-specific imprinted genes within the Kcnq1 domain. Imprinted genes are positive regulators of apoptosis, one of the forms of cell death related to cataract formation, and thus may provide novel therapeutic targets for cataract treatment. Here, we studied the role of non-coding RNAs(ncRNA) in cataract formation. Methods: Human lens epithelium cells (HLECs) were treated with H2O2, and the expression of KCNQ1OT1 and miR-214 was detected by qRT-PCR. The expression of caspase-1 was detected using qRT-PCR, western blot and immunostaining. To confirm our findings in cell cultures, we analysed KCNQ1OT1, miR-214, and caspase-1 expression in lens anterior capsules of both cataract patients and normal controls by qRT-PCR and western blot analysis. Results: We found that the expression of KCNQ1OT1 was increased in both human cataract lens anterior capsular samples and SRA01/04 cell lines treated with H2O2. Knockdown of KCNQ1OT1 expression significantly suppressed H2O2-induced SRA01/04 cell pyroptosis in vitro, which is the critical step in cataract formation. The expression of microRNA-214 (miR-214) was also decreased in cataract lens anterior capsular tissues and H2O2-induced SRA01/04 cell lines. Knockdown of KCNQ1OT1 significantly increased the expression of miR-214. Conclusions: We demonstrated for the first time that caspase-1 is a functional downstream target of miR-214, and knockdown of KCNQ1OT1 reduced the expression of caspase-1. These results provide evidence that the KCNQ1OT1-miR-214-caspase-1 regulatory network is a novel mechanism for promoting cataract formation. |
| first_indexed | 2024-12-12T20:49:46Z |
| format | Article |
| id | doaj.art-39c0002c0cdf4a15ae810ec9b6b9a827 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-12T20:49:46Z |
| publishDate | 2017-05-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-39c0002c0cdf4a15ae810ec9b6b9a8272022-12-22T00:12:27ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782017-05-0142129530510.1159/000477330477330Long Non-Coding RNA KCNQ1OT1 Promotes Cataractogenesis via miR-214 and Activation of the Caspase-1 PathwayXin JinHao JinYan ShiYiyuan GuoHong ZhangBackground/Aims: KCNQ1OT1 regulates the expression of tissue-specific imprinted genes within the Kcnq1 domain. Imprinted genes are positive regulators of apoptosis, one of the forms of cell death related to cataract formation, and thus may provide novel therapeutic targets for cataract treatment. Here, we studied the role of non-coding RNAs(ncRNA) in cataract formation. Methods: Human lens epithelium cells (HLECs) were treated with H2O2, and the expression of KCNQ1OT1 and miR-214 was detected by qRT-PCR. The expression of caspase-1 was detected using qRT-PCR, western blot and immunostaining. To confirm our findings in cell cultures, we analysed KCNQ1OT1, miR-214, and caspase-1 expression in lens anterior capsules of both cataract patients and normal controls by qRT-PCR and western blot analysis. Results: We found that the expression of KCNQ1OT1 was increased in both human cataract lens anterior capsular samples and SRA01/04 cell lines treated with H2O2. Knockdown of KCNQ1OT1 expression significantly suppressed H2O2-induced SRA01/04 cell pyroptosis in vitro, which is the critical step in cataract formation. The expression of microRNA-214 (miR-214) was also decreased in cataract lens anterior capsular tissues and H2O2-induced SRA01/04 cell lines. Knockdown of KCNQ1OT1 significantly increased the expression of miR-214. Conclusions: We demonstrated for the first time that caspase-1 is a functional downstream target of miR-214, and knockdown of KCNQ1OT1 reduced the expression of caspase-1. These results provide evidence that the KCNQ1OT1-miR-214-caspase-1 regulatory network is a novel mechanism for promoting cataract formation.http://www.karger.com/Article/FullText/477330CataractKCNQ1OT1miR-214Caspase-1Pyroptosis |
| spellingShingle | Xin Jin Hao Jin Yan Shi Yiyuan Guo Hong Zhang Long Non-Coding RNA KCNQ1OT1 Promotes Cataractogenesis via miR-214 and Activation of the Caspase-1 Pathway Cellular Physiology and Biochemistry Cataract KCNQ1OT1 miR-214 Caspase-1 Pyroptosis |
| title | Long Non-Coding RNA KCNQ1OT1 Promotes Cataractogenesis via miR-214 and Activation of the Caspase-1 Pathway |
| title_full | Long Non-Coding RNA KCNQ1OT1 Promotes Cataractogenesis via miR-214 and Activation of the Caspase-1 Pathway |
| title_fullStr | Long Non-Coding RNA KCNQ1OT1 Promotes Cataractogenesis via miR-214 and Activation of the Caspase-1 Pathway |
| title_full_unstemmed | Long Non-Coding RNA KCNQ1OT1 Promotes Cataractogenesis via miR-214 and Activation of the Caspase-1 Pathway |
| title_short | Long Non-Coding RNA KCNQ1OT1 Promotes Cataractogenesis via miR-214 and Activation of the Caspase-1 Pathway |
| title_sort | long non coding rna kcnq1ot1 promotes cataractogenesis via mir 214 and activation of the caspase 1 pathway |
| topic | Cataract KCNQ1OT1 miR-214 Caspase-1 Pyroptosis |
| url | http://www.karger.com/Article/FullText/477330 |
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