Molecular Pathogenesis of Gene Regulation by the <i>miR-150</i> Duplex: <i>miR-150-3p</i> Regulates <i>TNS4</i> in Lung Adenocarcinoma
Based on our miRNA expression signatures, we focused on <i>miR-150-5p</i> (the guide strand) and <i>miR-150-3p</i> (the passenger strand) to investigate their functional significance in lung adenocarcinoma (LUAD). Downregulation of <i>miR-150</i> duplex was confir...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/5/601 |
| _version_ | 1797708031282118656 |
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| author | Shunsuke Misono Naohiko Seki Keiko Mizuno Yasutaka Yamada Akifumi Uchida Hiroki Sanada Shogo Moriya Naoko Kikkawa Tomohiro Kumamoto Takayuki Suetsugu Hiromasa Inoue |
| author_facet | Shunsuke Misono Naohiko Seki Keiko Mizuno Yasutaka Yamada Akifumi Uchida Hiroki Sanada Shogo Moriya Naoko Kikkawa Tomohiro Kumamoto Takayuki Suetsugu Hiromasa Inoue |
| author_sort | Shunsuke Misono |
| collection | DOAJ |
| description | Based on our miRNA expression signatures, we focused on <i>miR-150-5p</i> (the guide strand) and <i>miR-150-3p</i> (the passenger strand) to investigate their functional significance in lung adenocarcinoma (LUAD). Downregulation of <i>miR-150</i> duplex was confirmed in LUAD clinical specimens. In vitro assays revealed that ectopic expression of <i>miR-150-5p</i> and <i>miR-150-3p</i> inhibited cancer cell malignancy. We performed genome-wide gene expression analyses and in silico database searches to identify their oncogenic targets in LUAD cells. A total of 41 and 26 genes were identified as <i>miR-150-5p</i> and <i>miR-150-3p</i> targets, respectively, and they were closely involved in LUAD pathogenesis. Among the targets, we investigated the oncogenic roles of tensin 4 (<i>TNS4</i>) because high expression of <i>TNS4</i> was strongly related to poorer prognosis of LUAD patients (disease-free survival: <i>p</i> = 0.0213 and overall survival: <i>p</i> = 0.0003). Expression of <i>TNS4</i> was directly regulated by <i>miR-150-3p</i> in LUAD cells. Aberrant expression of TNS4 was detected in LUAD clinical specimens and its aberrant expression increased the aggressiveness of LUAD cells. Furthermore, we identified genes downstream from <i>TNS4</i> that were associated with critical regulators of genomic stability. Our approach (discovery of anti-tumor miRNAs and their target RNAs for LUAD) will contribute to the elucidation of molecular networks involved in the malignant transformation of LUAD. |
| first_indexed | 2024-03-12T06:16:20Z |
| format | Article |
| id | doaj.art-099c08cb40de408b9c69ed0388dde5d1 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T06:16:20Z |
| publishDate | 2019-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-099c08cb40de408b9c69ed0388dde5d12023-09-03T02:32:15ZengMDPI AGCancers2072-66942019-04-0111560110.3390/cancers11050601cancers11050601Molecular Pathogenesis of Gene Regulation by the <i>miR-150</i> Duplex: <i>miR-150-3p</i> Regulates <i>TNS4</i> in Lung AdenocarcinomaShunsuke Misono0Naohiko Seki1Keiko Mizuno2Yasutaka Yamada3Akifumi Uchida4Hiroki Sanada5Shogo Moriya6Naoko Kikkawa7Tomohiro Kumamoto8Takayuki Suetsugu9Hiromasa Inoue10Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Functional Genomics, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, JapanDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Functional Genomics, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, JapanDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, JapanDepartment of Functional Genomics, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, JapanDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanBased on our miRNA expression signatures, we focused on <i>miR-150-5p</i> (the guide strand) and <i>miR-150-3p</i> (the passenger strand) to investigate their functional significance in lung adenocarcinoma (LUAD). Downregulation of <i>miR-150</i> duplex was confirmed in LUAD clinical specimens. In vitro assays revealed that ectopic expression of <i>miR-150-5p</i> and <i>miR-150-3p</i> inhibited cancer cell malignancy. We performed genome-wide gene expression analyses and in silico database searches to identify their oncogenic targets in LUAD cells. A total of 41 and 26 genes were identified as <i>miR-150-5p</i> and <i>miR-150-3p</i> targets, respectively, and they were closely involved in LUAD pathogenesis. Among the targets, we investigated the oncogenic roles of tensin 4 (<i>TNS4</i>) because high expression of <i>TNS4</i> was strongly related to poorer prognosis of LUAD patients (disease-free survival: <i>p</i> = 0.0213 and overall survival: <i>p</i> = 0.0003). Expression of <i>TNS4</i> was directly regulated by <i>miR-150-3p</i> in LUAD cells. Aberrant expression of TNS4 was detected in LUAD clinical specimens and its aberrant expression increased the aggressiveness of LUAD cells. Furthermore, we identified genes downstream from <i>TNS4</i> that were associated with critical regulators of genomic stability. Our approach (discovery of anti-tumor miRNAs and their target RNAs for LUAD) will contribute to the elucidation of molecular networks involved in the malignant transformation of LUAD.https://www.mdpi.com/2072-6694/11/5/601MicroRNA<i>miR-150-5p</i><i>miR-150-3p</i>lung adenocarcinoma<i>TNS4</i> |
| spellingShingle | Shunsuke Misono Naohiko Seki Keiko Mizuno Yasutaka Yamada Akifumi Uchida Hiroki Sanada Shogo Moriya Naoko Kikkawa Tomohiro Kumamoto Takayuki Suetsugu Hiromasa Inoue Molecular Pathogenesis of Gene Regulation by the <i>miR-150</i> Duplex: <i>miR-150-3p</i> Regulates <i>TNS4</i> in Lung Adenocarcinoma Cancers MicroRNA <i>miR-150-5p</i> <i>miR-150-3p</i> lung adenocarcinoma <i>TNS4</i> |
| title | Molecular Pathogenesis of Gene Regulation by the <i>miR-150</i> Duplex: <i>miR-150-3p</i> Regulates <i>TNS4</i> in Lung Adenocarcinoma |
| title_full | Molecular Pathogenesis of Gene Regulation by the <i>miR-150</i> Duplex: <i>miR-150-3p</i> Regulates <i>TNS4</i> in Lung Adenocarcinoma |
| title_fullStr | Molecular Pathogenesis of Gene Regulation by the <i>miR-150</i> Duplex: <i>miR-150-3p</i> Regulates <i>TNS4</i> in Lung Adenocarcinoma |
| title_full_unstemmed | Molecular Pathogenesis of Gene Regulation by the <i>miR-150</i> Duplex: <i>miR-150-3p</i> Regulates <i>TNS4</i> in Lung Adenocarcinoma |
| title_short | Molecular Pathogenesis of Gene Regulation by the <i>miR-150</i> Duplex: <i>miR-150-3p</i> Regulates <i>TNS4</i> in Lung Adenocarcinoma |
| title_sort | molecular pathogenesis of gene regulation by the i mir 150 i duplex i mir 150 3p i regulates i tns4 i in lung adenocarcinoma |
| topic | MicroRNA <i>miR-150-5p</i> <i>miR-150-3p</i> lung adenocarcinoma <i>TNS4</i> |
| url | https://www.mdpi.com/2072-6694/11/5/601 |
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