Identification of Tumor-Suppressive <i>miR-30a-3p</i> Controlled Genes: <i>ANLN</i> as a Therapeutic Target in Breast Cancer
Our recently created RNA-sequence-based microRNA (miRNA) expression signature in breast cancer clinical specimens revealed that some <i>miR-30</i> family members were significantly downregulated in cancer tissues. Based on TCGA database analyses, we observed that among the <i>miR-3...
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2024-11-01
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| author | Reiko Mitsueda Ayako Nagata Hiroko Toda Yuya Tomioka Ryutaro Yasudome Mayuko Kato Yoshiaki Shinden Akihiro Nakajo Naohiko Seki |
| author_facet | Reiko Mitsueda Ayako Nagata Hiroko Toda Yuya Tomioka Ryutaro Yasudome Mayuko Kato Yoshiaki Shinden Akihiro Nakajo Naohiko Seki |
| author_sort | Reiko Mitsueda |
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| description | Our recently created RNA-sequence-based microRNA (miRNA) expression signature in breast cancer clinical specimens revealed that some <i>miR-30</i> family members were significantly downregulated in cancer tissues. Based on TCGA database analyses, we observed that among the <i>miR-30</i> family members, <i>miR-30a-3p</i> (the passenger strand derived from pre-<i>miR-30a</i>) was significantly downregulated in breast cancer (BC) clinical specimens, and its low expression predicted worse prognoses. Ectopic expression assays showed that <i>miR-30a-3p</i> transfected cancer cells (MDA-MB-157 and MDA-MB-231) had their aggressive phenotypes significantly suppressed, e.g., their proliferation, migration, and invasion abilities. These data indicated that <i>miR-30a-3p</i> acted as a tumor-suppressive miRNA in BC cells. Our subsequent search for <i>miR-30a-3p</i> controlled molecular networks in BC cells yielded a total of 189 genes. Notably, among those 189 genes, cell-cycle-related genes (<i>ANLN</i>, <i>MKI67</i>, <i>CCNB1</i>, <i>NCAPG</i>, <i>ZWINT</i>, <i>E2F7</i>, <i>PDS5A</i>, <i>RIF1</i>, <i>BIRC5</i>, <i>MAD2L1</i>, <i>CACUL1</i>, <i>KIF23</i>, <i>UBE2S</i>, <i>EML4</i>, <i>SEPT10</i>, <i>CLTC</i>, and <i>PCNP</i>) were enriched according to a GeneCodis 4 database analysis. Moreover, the overexpression of four genes (<i>ANLN</i>, <i>CCNB1</i>, <i>BIRC5</i>, and <i>KIF23</i>) significantly predicted worse prognoses for patients with BC according to TCGA analyses. Finally, our assays demonstrated that the overexpression of <i>ANLN</i> had cancer-promoting functions in BC cells. The involvement of <i>miR-30a-3p</i> (the passenger strand) in BC molecular pathogenesis is a new concept in cancer research, and the outcomes of our study strongly indicate the importance of analyzing passenger strands of miRNAs in BC cells. |
| format | Article |
| id | doaj-art-9b08a4f5b1d840fd82e83869b71863c0 |
| institution | Kabale University |
| issn | 2311-553X |
| language | English |
| publishDate | 2024-11-01 |
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| spelling | doaj-art-9b08a4f5b1d840fd82e83869b71863c02024-12-27T14:43:39ZengMDPI AGNon-Coding RNA2311-553X2024-11-011066010.3390/ncrna10060060Identification of Tumor-Suppressive <i>miR-30a-3p</i> Controlled Genes: <i>ANLN</i> as a Therapeutic Target in Breast CancerReiko Mitsueda0Ayako Nagata1Hiroko Toda2Yuya Tomioka3Ryutaro Yasudome4Mayuko Kato5Yoshiaki Shinden6Akihiro Nakajo7Naohiko Seki8Department of Breast and Thyroid Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Breast and Thyroid Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Breast and Thyroid Surgery, 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 Breast and Thyroid Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Functional Genomics, Chiba University Graduate School of Medicine, Chiba 260-8670, JapanDepartment of Breast and Thyroid Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Breast and Thyroid Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Functional Genomics, Chiba University Graduate School of Medicine, Chiba 260-8670, JapanOur recently created RNA-sequence-based microRNA (miRNA) expression signature in breast cancer clinical specimens revealed that some <i>miR-30</i> family members were significantly downregulated in cancer tissues. Based on TCGA database analyses, we observed that among the <i>miR-30</i> family members, <i>miR-30a-3p</i> (the passenger strand derived from pre-<i>miR-30a</i>) was significantly downregulated in breast cancer (BC) clinical specimens, and its low expression predicted worse prognoses. Ectopic expression assays showed that <i>miR-30a-3p</i> transfected cancer cells (MDA-MB-157 and MDA-MB-231) had their aggressive phenotypes significantly suppressed, e.g., their proliferation, migration, and invasion abilities. These data indicated that <i>miR-30a-3p</i> acted as a tumor-suppressive miRNA in BC cells. Our subsequent search for <i>miR-30a-3p</i> controlled molecular networks in BC cells yielded a total of 189 genes. Notably, among those 189 genes, cell-cycle-related genes (<i>ANLN</i>, <i>MKI67</i>, <i>CCNB1</i>, <i>NCAPG</i>, <i>ZWINT</i>, <i>E2F7</i>, <i>PDS5A</i>, <i>RIF1</i>, <i>BIRC5</i>, <i>MAD2L1</i>, <i>CACUL1</i>, <i>KIF23</i>, <i>UBE2S</i>, <i>EML4</i>, <i>SEPT10</i>, <i>CLTC</i>, and <i>PCNP</i>) were enriched according to a GeneCodis 4 database analysis. Moreover, the overexpression of four genes (<i>ANLN</i>, <i>CCNB1</i>, <i>BIRC5</i>, and <i>KIF23</i>) significantly predicted worse prognoses for patients with BC according to TCGA analyses. Finally, our assays demonstrated that the overexpression of <i>ANLN</i> had cancer-promoting functions in BC cells. The involvement of <i>miR-30a-3p</i> (the passenger strand) in BC molecular pathogenesis is a new concept in cancer research, and the outcomes of our study strongly indicate the importance of analyzing passenger strands of miRNAs in BC cells.https://www.mdpi.com/2311-553X/10/6/60breast cancermicroRNA<i>miR-30a-3p</i>passenger strand<i>ANLN</i> |
| spellingShingle | Reiko Mitsueda Ayako Nagata Hiroko Toda Yuya Tomioka Ryutaro Yasudome Mayuko Kato Yoshiaki Shinden Akihiro Nakajo Naohiko Seki Identification of Tumor-Suppressive <i>miR-30a-3p</i> Controlled Genes: <i>ANLN</i> as a Therapeutic Target in Breast Cancer Non-Coding RNA breast cancer microRNA <i>miR-30a-3p</i> passenger strand <i>ANLN</i> |
| title | Identification of Tumor-Suppressive <i>miR-30a-3p</i> Controlled Genes: <i>ANLN</i> as a Therapeutic Target in Breast Cancer |
| title_full | Identification of Tumor-Suppressive <i>miR-30a-3p</i> Controlled Genes: <i>ANLN</i> as a Therapeutic Target in Breast Cancer |
| title_fullStr | Identification of Tumor-Suppressive <i>miR-30a-3p</i> Controlled Genes: <i>ANLN</i> as a Therapeutic Target in Breast Cancer |
| title_full_unstemmed | Identification of Tumor-Suppressive <i>miR-30a-3p</i> Controlled Genes: <i>ANLN</i> as a Therapeutic Target in Breast Cancer |
| title_short | Identification of Tumor-Suppressive <i>miR-30a-3p</i> Controlled Genes: <i>ANLN</i> as a Therapeutic Target in Breast Cancer |
| title_sort | identification of tumor suppressive i mir 30a 3p i controlled genes i anln i as a therapeutic target in breast cancer |
| topic | breast cancer microRNA <i>miR-30a-3p</i> passenger strand <i>ANLN</i> |
| url | https://www.mdpi.com/2311-553X/10/6/60 |
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