{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:01:31Z","timestamp":1790359291996,"version":"4.1.0"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Angiogenesis plays a crucial role in cancer metastasis as tumors need to establish an increased blood supply to satisfy the demand for oxygen and nutrients. Numerous genes regulate this process, and various mechanisms including microRNAs regulate the expression of these genes. In the current study, we hypothesized that miR-6756 and miR-3190 regulate angiogenic mediators such as transcription factor ETS-related gene (ERG). Detailed bioinformatics analyses were performed to locate binding sites of miR-6756 and miR-3190 on ERG mRNA. miR-6756 and miR-3190 were cloned and overexpressed in primary endothelial cells to analyze ERG expression. To evaluate ERG activity reporter assays were performed in response to miR-6756 and miR-3190 over-expression. The effects of miRs on angiogenesis were measured by cell migration rate using the scratch assay. The expression of angiogenic targets of ERG was analyzed through qPCR with and without miR-6756 and miR-3190 overexpression. Lastly, VE-cadherin; an endothelial-specific ERG target was analyzed after miRs overexpression. Bioinformatics analyses showed that both miR-6756 and miR-3190 each have three binding sites on the mRNA of ERG. ERG expression at both mRNA (\n                    <jats:italic>p\u2009&lt;\u20090.001<\/jats:italic>\n                    ) and the protein level (\n                    <jats:italic>p\u2009&lt;\u20090.001<\/jats:italic>\n                    ) was significantly reduced after miR-6756 and miR-3190 overexpression. Also, the transcriptional activity of ERG significantly reduced (p\u2009&lt;\u20090.05) in response to miRs overexpression. Cell migration rate (\n                    <jats:italic>p\u2009&lt;\u20090.001<\/jats:italic>\n                    ) and ERG angiogenic target genes were also decreased significantly (\n                    <jats:italic>p\u2009&lt;\u20090.001<\/jats:italic>\n                    ). VE-cadherin also showed significantly reduced expression and activity after miR-6756 and miR-3190 over-expression. This study indicates that miR-6756 and miR-3190 can regulate ERG expression and its target genes.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0358739","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:35:09Z","timestamp":1790357709000},"page":"e0358739","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of angiogenic transcription factor ERG via miR-6756 and miR-3190"],"prefix":"10.1371","volume":"21","author":[{"given":"Sidra","family":"Mumtaz","sequence":"first","affiliation":[{"name":"GC University","place":["Lahore, Pakistan"],"department":["Department of Zoology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Usman","family":"Rashid","sequence":"additional","affiliation":[{"name":"Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH & RC)","place":["Lahore, Pakistan"],"department":["Department of Basic Sciences Research"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safir Ullah","family":"Khan","sequence":"additional","affiliation":[{"name":"Moores Cancer Center, University of California","place":["San Diego, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6454-1525","authenticated-orcid":true,"given":"Naila","family":"Malkani","sequence":"additional","affiliation":[{"name":"GC University","place":["Lahore, Pakistan"],"department":["Department of Zoology"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"issue":"1","key":"pone.0358739.ref001","doi-asserted-by":"crossref","first-page":"84","DOI":"10.3390\/jcm9010084","article-title":"Tumor Angiogenesis and Anti-Angiogenic Strategies for Cancer Treatment","volume":"9","author":"RI 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