{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:59:18Z","timestamp":1773291558639,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2011,9,26]],"date-time":"2011-09-26T00:00:00Z","timestamp":1316995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Hodgkin's lymphoma (HL) is a B cell\u2010derived lymphoma characterized by a minority of malignant Hodgkin Reed\u2013Sternberg (HRS) cells that have lost their normal B cell phenotype. Alterations in the cell cycle and apoptosis pathways might contribute to their resistance to apoptosis and sustained cell cycle progression. A key player in both cell cycle arrest and apoptosis is\n                    <jats:italic>CDKN1A<\/jats:italic>\n                    , encoding p21\n                    <jats:styled-content>\n                      $^{{\\rm{waf\/cip1}}}$\n                      <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tex2gif-ueqn-1.gif\" xlink:title=\"equation image\"\/>\n                    <\/jats:styled-content>\n                    (p21). P21 is regulated by p53 and can function as a cell cycle inhibitor when in the nucleus or as an apoptosis inhibitor when localized in the cytoplasm. We observed expression of p53, p21 and p\u2010p21 in a variable number of HRS cells in 24 of 40 cases. Expression of miR\u201017 and miR\u2010106a was detected in HRS cells of 10 HL cases. MiR\u201017\/106b seed family members,\n                    <jats:italic>CDKN1A<\/jats:italic>\n                    RNA and p21 protein levels were variable in HL cell lines. We showed effective targeting of the\n                    <jats:italic>CDKN1A<\/jats:italic>\n                    3\u2032 UTR by miR\u201017\/106b in HL cell lines in a luciferase reporter assay and up\u2010regulation of p21 protein levels upon anti\u2010miR\u201017 treatment of KM\u2010H2 cells. Functional studies indicated a p21\u2010mediated G\n                    <jats:sub>1<\/jats:sub>\n                    arrest after miR\u201017\/106b down\u2010regulation in KM\u2010H2, whereas no G\n                    <jats:sub>1<\/jats:sub>\n                    arrest was observed for U\u2010HO1 and L428. This difference could not be explained by differences in the 3\u2032 UTR, the cellular location of p21 or expression variation during cell cycle progression. A strong correlation was observed for the miR\u201017\/106b:\n                    <jats:italic>CDKN1A<\/jats:italic>\n                    ratio and the responsiveness to miR\u201017 inhibition, ie a low ratio in KM\u2010H2 and an extremely high ratio in the two unresponsive HL cell lines. In conclusion, we show that miR\u201017\/106b regulates p21 protein levels in HL and that the effect of miR\u201017\/106b\u2010mediated inhibition depends on the miRNA : target gene ratio. Thus, in HL high miR\u201017\/106b expression contributes to a dysfunctional p53 pathway and thereby also to the malignant phenotype. Copyright \u00a9 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.2958","type":"journal-article","created":{"date-parts":[[2011,6,30]],"date-time":"2011-06-30T08:08:33Z","timestamp":1309421313000},"page":"609-617","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["MiR\u201017\/106b seed family regulates p21 in Hodgkin's lymphoma"],"prefix":"10.1002","volume":"225","author":[{"given":"Johan 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