{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:22:32Z","timestamp":1791073352415,"version":"4.1.0"},"reference-count":43,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,6,25]]},"abstract":"<jats:p>\n                    Polycystic kidney disease (PKD), the most common genetic cause of chronic kidney failure, is characterized by the presence of numerous, progressively enlarging fluid-filled cysts in the renal parenchyma. The cysts arise from renal tubules and are lined by abnormally functioning and hyperproliferative epithelial cells. Despite recent progress, no Food and Drug Administration-approved therapy is available to retard cyst growth. MicroRNAs (miRNAs) are short noncoding RNAs that inhibit posttranscriptional gene expression. Dysregulated miRNA expression is observed in PKD, but whether miRNAs are directly involved in kidney cyst formation and growth is not known. Here, we show that miR-17\u223c92, an oncogenic miRNA cluster, is up-regulated in mouse models of PKD. Kidney-specific transgenic overexpression of miR-17\u223c92 produces kidney cysts in mice. Conversely, kidney-specific inactivation of miR-17\u223c92 in a mouse model of PKD retards kidney cyst growth, improves renal function, and prolongs survival. miR-17\u223c92 may mediate these effects by promoting proliferation and through posttranscriptional repression of PKD genes\n                    <jats:italic>Pkd1<\/jats:italic>\n                    ,\n                    <jats:italic>Pkd2<\/jats:italic>\n                    , and hepatocyte nuclear factor-\n                    <jats:italic>1<\/jats:italic>\n                    \u03b2. These studies demonstrate a pathogenic role of miRNAs in mouse models of PKD and identify miR-17\u223c92 as a therapeutic target in PKD. Our results also provide a unique hypothesis for disease progression in PKD involving miRNAs and regulation of PKD gene dosage.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1301693110","type":"journal-article","created":{"date-parts":[[2013,6,13]],"date-time":"2013-06-13T00:05:51Z","timestamp":1371081951000},"page":"10765-10770","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":171,"title":["miR-17\u223c92 miRNA cluster promotes kidney cyst growth in polycystic kidney disease"],"prefix":"10.1073","volume":"110","author":[{"given":"Vishal","family":"Patel","sequence":"first","affiliation":[{"name":"Departments of aInternal Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Williams","sequence":"additional","affiliation":[{"name":"Departments of aInternal Medicine 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