Silencing of lncRNA MIR497HG via CRISPR/Cas13d Induces Bladder Cancer Progression Through Promoting the Crosstalk Between Hippo/Yap and TGF-β/Smad Signaling
A subset of long non-coding RNAs (lncRNAs), categorized as miRNA-host gene lncRNAs (lnc-miRHGs), is processed to produce miRNAs and involved in cancer progression. This work aimed to investigate the influences and the molecular mechanisms of lnc-miRHGs MIR497HG in bladder cancer (BCa). The miR-497 a...
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| Language: | English |
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2020.616768/full |
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| author | Changshui Zhuang Ying Liu Shengqiang Fu Chaobo Yuan Jingwen Luo Xueting Huang Weifeng Yang Wuwei Xie Chengle Zhuang |
| author_facet | Changshui Zhuang Ying Liu Shengqiang Fu Chaobo Yuan Jingwen Luo Xueting Huang Weifeng Yang Wuwei Xie Chengle Zhuang |
| author_sort | Changshui Zhuang |
| collection | DOAJ |
| description | A subset of long non-coding RNAs (lncRNAs), categorized as miRNA-host gene lncRNAs (lnc-miRHGs), is processed to produce miRNAs and involved in cancer progression. This work aimed to investigate the influences and the molecular mechanisms of lnc-miRHGs MIR497HG in bladder cancer (BCa). The miR-497 and miR-195 were derived from MIR497HG. We identified that lnc-miRHG MIR497HG and two harbored miRNAs, miR-497 and miR-195, were downregulated in BCa by analyzing The Cancer Genome Atlas and our dataset. Silencing of MIR497HG by CRISPR/Cas13d in BCa cell line 5637 promoted cell growth, migration, and invasion in vitro. Conversely, overexpression of MIR497HG suppressed cell progression in BCa cell line T24. MiR-497/miR-195 mimics rescued significantly the oncogenic roles of knockdown of MIR497HG by CRISPR/Cas13d in BCa. Mechanistically, miR-497 and miR-195 co-ordinately suppressed multiple key components in Hippo/Yap and transforming growth factor β signaling and particularly attenuated the interaction between Yap and Smad3. In addition, E2F4 was proven to be critical for silencing MIR497HG transcription in BCa cells. In short, we propose for the first time to reveal the function and mechanisms of MIR497HG in BCa. Blocking the pathological process may be a potential strategy for the treatment of BCa. |
| first_indexed | 2024-12-17T07:05:20Z |
| format | Article |
| id | doaj.art-287c58cd50be438fafda418cc9105037 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-17T07:05:20Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-287c58cd50be438fafda418cc91050372022-12-21T21:59:11ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2020-12-01710.3389/fmolb.2020.616768616768Silencing of lncRNA MIR497HG via CRISPR/Cas13d Induces Bladder Cancer Progression Through Promoting the Crosstalk Between Hippo/Yap and TGF-β/Smad SignalingChangshui Zhuang0Ying Liu1Shengqiang Fu2Chaobo Yuan3Jingwen Luo4Xueting Huang5Weifeng Yang6Wuwei Xie7Chengle Zhuang8Department of Urology, Union Shenzhen Hospital, Huazhong University of Science and Technology, Shenzhen, ChinaShenzhen People’s Hospital, The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen, ChinaDepartment of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaEmergency Department, Union Shenzhen Hospital, Huazhong University of Science and Technology, Shenzhen, ChinaDepartment of Thoracic Surgery, Union Shenzhen Hospital, Huazhong University of Science and Technology, Shenzhen, ChinaShenzhen Yantian District People’s Hospital, Shenzhen, ChinaDepartment of Urology, Union Shenzhen Hospital, Huazhong University of Science and Technology, Shenzhen, ChinaDepartment of Urology, Peking University Shenzhen Hospital, Shenzhen, ChinaDepartment of Urology, Peking University Shenzhen Hospital, Shenzhen, ChinaA subset of long non-coding RNAs (lncRNAs), categorized as miRNA-host gene lncRNAs (lnc-miRHGs), is processed to produce miRNAs and involved in cancer progression. This work aimed to investigate the influences and the molecular mechanisms of lnc-miRHGs MIR497HG in bladder cancer (BCa). The miR-497 and miR-195 were derived from MIR497HG. We identified that lnc-miRHG MIR497HG and two harbored miRNAs, miR-497 and miR-195, were downregulated in BCa by analyzing The Cancer Genome Atlas and our dataset. Silencing of MIR497HG by CRISPR/Cas13d in BCa cell line 5637 promoted cell growth, migration, and invasion in vitro. Conversely, overexpression of MIR497HG suppressed cell progression in BCa cell line T24. MiR-497/miR-195 mimics rescued significantly the oncogenic roles of knockdown of MIR497HG by CRISPR/Cas13d in BCa. Mechanistically, miR-497 and miR-195 co-ordinately suppressed multiple key components in Hippo/Yap and transforming growth factor β signaling and particularly attenuated the interaction between Yap and Smad3. In addition, E2F4 was proven to be critical for silencing MIR497HG transcription in BCa cells. In short, we propose for the first time to reveal the function and mechanisms of MIR497HG in BCa. Blocking the pathological process may be a potential strategy for the treatment of BCa.https://www.frontiersin.org/articles/10.3389/fmolb.2020.616768/fullbladder cancerMIR497HGCRISPR/Cas13dYapTGF-β |
| spellingShingle | Changshui Zhuang Ying Liu Shengqiang Fu Chaobo Yuan Jingwen Luo Xueting Huang Weifeng Yang Wuwei Xie Chengle Zhuang Silencing of lncRNA MIR497HG via CRISPR/Cas13d Induces Bladder Cancer Progression Through Promoting the Crosstalk Between Hippo/Yap and TGF-β/Smad Signaling Frontiers in Molecular Biosciences bladder cancer MIR497HG CRISPR/Cas13d Yap TGF-β |
| title | Silencing of lncRNA MIR497HG via CRISPR/Cas13d Induces Bladder Cancer Progression Through Promoting the Crosstalk Between Hippo/Yap and TGF-β/Smad Signaling |
| title_full | Silencing of lncRNA MIR497HG via CRISPR/Cas13d Induces Bladder Cancer Progression Through Promoting the Crosstalk Between Hippo/Yap and TGF-β/Smad Signaling |
| title_fullStr | Silencing of lncRNA MIR497HG via CRISPR/Cas13d Induces Bladder Cancer Progression Through Promoting the Crosstalk Between Hippo/Yap and TGF-β/Smad Signaling |
| title_full_unstemmed | Silencing of lncRNA MIR497HG via CRISPR/Cas13d Induces Bladder Cancer Progression Through Promoting the Crosstalk Between Hippo/Yap and TGF-β/Smad Signaling |
| title_short | Silencing of lncRNA MIR497HG via CRISPR/Cas13d Induces Bladder Cancer Progression Through Promoting the Crosstalk Between Hippo/Yap and TGF-β/Smad Signaling |
| title_sort | silencing of lncrna mir497hg via crispr cas13d induces bladder cancer progression through promoting the crosstalk between hippo yap and tgf β smad signaling |
| topic | bladder cancer MIR497HG CRISPR/Cas13d Yap TGF-β |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2020.616768/full |
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