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Hokkaido University Collection of Scholarly and Academic Papers >
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Stable duplex-linked antisense targeting miR-148a inhibits breast cancer cell proliferation
| Title: | Stable duplex-linked antisense targeting miR-148a inhibits breast cancer cell proliferation |
| Authors: | Okumura, Sho Browse this author | | Hirano, Yu Browse this author | | Komatsu, Yasuo Browse this author |
| Issue Date: | 1-Jun-2021 |
| Publisher: | Nature Research |
| Journal Title: | Scientific reports |
| Volume: | 11 |
| Issue: | 1 |
| Start Page: | 11467 |
| Publisher DOI: | 10.1038/s41598-021-90972-3 |
| Abstract: | MicroRNAs (miRNAs) regulate cancer cell proliferation by binding directly to the untranslated regions of messenger RNA (mRNA). MicroRNA-148a (miR-148a) is expressed at low levels in breast cancer (BC). However, little attention has been paid to the sequestration of miR-148a. Here, we performed a knockdown of miR-148a using anti-miRNA oligonucleotides (AMOs) and investigated the effect on BC cell proliferation. BC cell proliferation was significantly suppressed by AMO flanked by interstrand cross-linked duplexes (CL-AMO), whereas single-stranded and commercially available AMOs had no effect. The suppression was caused by sequestering specifically miR-148a. Indeed, miR-148b, another member of the miR-148 family, was not affected. Importantly, the downregulation of miR-148a induced a greater and longer-lasting inhibition of BC cell proliferation than the targeting of oncogenic microRNA-21 (miR-21) did. We identified thioredoxin-interacting protein (TXNIP), a tumor suppressor gene, as a target of miR-148a and showed that CL-AMO provoked an increase in TXNIP mRNA expression. This study provide evidence that lowly expressed miRNAs such as miR-148a have an oncogenic function and might be a promising target for cancer treatment. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/82198 |
| Appears in Collections: | 生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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