{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T06:48:08Z","timestamp":1747205288308,"version":"3.40.5"},"posted":{"date-parts":[[2020,8,13]]},"group-title":"In Review","reference-count":0,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T00:00:00Z","timestamp":1597276800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2020,7,22]]},"abstract":"<title>Abstract<\/title>\n        <p><bold>Introduction:<\/bold> Breast cancer is the most frequently diagnosed malignancy among women. However, the role of microRNA expression in breast cancer progression is not fully understood. In this study we examined predictive interactions between differentially expressed miRNAs and mRNAs in breast cancer cell lines representative of the common molecular subtypes. Integrative bioinformatics analysis identified miR-193 and miR-210 as potential regulatory biomarkers of mRNA in breast cancer. Several recent studies have investigated these miRNAs in a broad range of tumors, but the mechanism of their involvement in cancer progression has not previously been investigated. <bold>Methods<\/bold>: The miRNA-mRNA interactions in breast cancer cell lines were identified by parallel expression analysis and miRNA target prediction programs. The expression profiles of mRNA and miRNAs from luminal (MCF-7, MCF-7\/AZ and T47D), HER2 (BT20 and SK-BR3) and triple negative subtypes (Hs578T e MDA-MB-231) could be clearly separated by unsupervised analysis using HB4A cell line as a control. Breast cancer miRNA data from TCGA patients were grouped according to molecular subtypes and then used to validate these findings. Expression of miR-193 and miR-210 was investigated by miRNA transient silencing assays using the MCF7, BT20 and MDA-MB-231 cell lines. Functional studies included, xCELLigence system, ApoTox-Glo triplex, flow cytometry and transwell assays were performed to determine cell proliferation, cytotoxicity, apoptosis, migration and invasion, respectively. <bold>Results:<\/bold> The most evident effects were associated with cell proliferation after miR-210 silencing in triple negative subtype cell line MDA-MB-231. Using <italic>in silico<\/italic> prediction algorithms, <italic>TNFRSF10<\/italic> was identified as one of the potential downstream targets for both miRNAs. The <italic>TNFRSF10C<\/italic> and <italic>TNFRSF10D<\/italic> mRNA expression inversely correlated with the expression levels of miR-193 and miR210 in breast cell lines and breast cancer patients, respectively. Other potential regulated genes whose expression also inversely correlated with both miRNAs were <italic>CCND1<\/italic>, a mediator on invasion and metastasis, and the tumor suppressor gene <italic>RUNX3<\/italic>. <bold>Conclusion<\/bold>: In summary, our findings identify miR-193 and miR-210 as potential regulatory miRNA in different molecular subtypes of breast cancer and suggest that miR-210 may have specific role in MDA-MB-231 proliferation. Our results highlight important new downstream regulated targets that may serve as promising therapeutic pathways for aggressive breast cancers.<\/p>","DOI":"10.21203\/rs.3.rs-47634\/v1","type":"posted-content","created":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T16:53:30Z","timestamp":1597337610000},"source":"Crossref","is-referenced-by-count":0,"title":["Integrative analysis of mRNA and miRNA pro\ufb01les identifies miR-193 and miR-210 as potential regulatory biomarkers in di\ufb00erent molecular subtypes of breast cancer"],"prefix":"10.21203","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4731-2082","authenticated-orcid":false,"given":"Adriane Feijo","family":"Evangelista","sequence":"first","affiliation":[{"name":"Barretos Cancer Hospital"}]},{"given":"Renato J","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Barretos Cancer Hospital"}]},{"given":"Viviane A O","family":"Silva","sequence":"additional","affiliation":[{"name":"Barretos Cancer Hospital"}]},{"given":"Rene A D C","family":"Vieira","sequence":"additional","affiliation":[{"name":"Barretos Cancer Hospital"}]},{"given":"Rui M","family":"Reis","sequence":"additional","affiliation":[{"name":"Barretos Cancer Hospital"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5616-6710","authenticated-orcid":false,"given":"Marcia M C","family":"Marques","sequence":"additional","affiliation":[{"name":"Barretos Cancer Hospital"}]}],"member":"297","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/www.researchsquare.com\/article\/rs-47634\/v1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.researchsquare.com\/article\/rs-47634\/v1.html","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T22:51:09Z","timestamp":1659048669000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.researchsquare.com\/article\/rs-47634\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,13]]},"references-count":0,"URL":"https:\/\/doi.org\/10.21203\/rs.3.rs-47634\/v1","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1186\/s12885-020-07731-2","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2020,8,13]]},"subtype":"preprint"}}