Identification of Tumor-Suppressive <i>miR-30a-3p</i> Controlled Genes: <i>ANLN</i> as a Therapeutic Target in Breast Cancer

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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Main Authors: Reiko Mitsueda, Ayako Nagata, Hiroko Toda, Yuya Tomioka, Ryutaro Yasudome, Mayuko Kato, Yoshiaki Shinden, Akihiro Nakajo, Naohiko Seki
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Non-Coding RNA
Subjects:
breast cancer
microRNA
<i>miR-30a-3p</i>
passenger strand
<i>ANLN</i>
Online Access:https://www.mdpi.com/2311-553X/10/6/60
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Summary: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.
ISSN:2311-553X

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