{"id":1304,"date":"2017-07-07T11:44:24","date_gmt":"2017-07-07T11:44:24","guid":{"rendered":"http:\/\/www.virologyhighlights.com\/?p=1304"},"modified":"2018-05-25T08:33:23","modified_gmt":"2018-05-25T08:33:23","slug":"perturbation-of-drosha-and-dicer-expression-by-human-papillomavirus-16-oncoproteins","status":"publish","type":"post","link":"https:\/\/www.elsevierblogs.com\/virology\/perturbation-of-drosha-and-dicer-expression-by-human-papillomavirus-16-oncoproteins\/","title":{"rendered":"Perturbation of DROSHA and DICER expression by human papillomavirus 16 oncoproteins"},"content":{"rendered":"

Read the full article on ScienceDirect.<\/a><\/h3>\n

DROSHA frequently overexpressed due to gene amplification<\/h2>\n

Text by Mallory Harden and Karl Munger
\n<\/em><\/p>\n

High-risk human papillomaviruses (HPV) are best known as the causative agents of cervical cancers.\u00a0 However, these viruses also cause several other human cancers.\u00a0 The two viral oncoproteins, E6 and E7, are consistently expressed in HPV-associated cancers. \u00a0Our study focuses on the most frequently detected high-risk HPV type, HPV16, and how the E6 and E7 oncoproteins alter small, non-coding RNAs called microRNAs (miRs).\u00a0 Most HPVs do not encode their own miRs, however, it is well known that HPVs alter expression of host miRs.\u00a0 In particular, we, and others, have shown that miR expression is perturbed when E6 and E7 are expressed.\u00a0 A question that has not been well studied, however, is how E6 and E7 alter host miR expression.\u00a0 There are likely several mechanisms by which the oncoproteins alter miR expression but, in this study, we show the E6 and E7 alter expression of key miR biogenesis enzymes.<\/p>\n

The idea for this study came from evidence in the literature that the miR biogenesis pathway is dysregulated in human cancers. Given that high-risk HPVs cause human cancers through E6 and E7 oncoprotein expression, we hypothesized that one mechanism by which HPV16 E6\/E7 may alter host miR expression was manipulation of the miR biogenesis pathway.\u00a0 We utilized primary epithelial cells derived from neonatal human foreskins for our studies. \u00a0We use these cells as they are the biologically relevant targets of HPV infection in males.\u00a0 However, these cells are much more difficult to work with as they take a long time to generate, they do not grow quickly and they can only be used in experiments for a short number of passages. \u00a0Additionally, these cells are generated from three or more different patient samples each time they are isolated, resulting in quite a bit of genetic diversity.\u00a0 These problems had to be overcome in many of the experiments in this study.<\/p>\n

The biggest surprise we encountered along the way was that our experiments supported our initial hypothesis.\u00a0 Hypotheses are always to be tested and, even when the experimental data do not support the hypothesis, the results can be interesting. However, we are excited and intrigued by the results that manipulation of miR biosynthesis enzymes may be one of the mechanisms by which HPV E6\/E7 expression changes the abundance of cellular miRs. Future studies will be focused on uncovering the mechanistic basis for this finding.\"Virology<\/p>\n

Figure legend<\/h3>\n

Perturbation of expression of key microRNA biogenesis enzymes, DROSHA and DICER, is one mechanism the Human Papillomavirus 16 oncoproteins utilize to alter microRNA expression.<\/p>\n

Introducing the authors<\/h3>\n

\"hardenmunger\"<\/p>\n

Pictured are Mallory Harden and Karl Munger from the Karl Munger Laboratory, Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA, USA<\/p>\n

About the research<\/h3>\n

Perturbation of DROSHA and DICER expression by human papillomavirus 16 oncoproteins<\/a>
\nMallory E. Harden, Karl Munger
\nVirology<\/em>, Volume 507, July 2017, Pages 192\u2013198<\/p>\n

 <\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

Read the full article on ScienceDirect. DROSHA frequently overexpressed due to gene amplification Text by Mallory Harden and Karl Munger High-risk human papillomaviruses (HPV) are best known as the causative agents of cervical cancers.\u00a0 However, these viruses also cause several other human cancers.\u00a0 The two viral oncoproteins, E6 and E7, are consistently expressed in HPV-associated Read More…<\/a><\/p>\n","protected":false},"author":1,"featured_media":1307,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[5,630],"tags":[762,1094,1093,1090,35,1089,34,1092,1091,1088,1118],"class_list":["post-1304","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-highlighted-article","category-virus-host-biology","tag-cancer","tag-dicer-expression","tag-drosha-expression","tag-e6e7-expression","tag-hpv","tag-hpv16","tag-human-papillomavirus","tag-micrornas","tag-mirs","tag-oncoproteins","tag-tufts-university-school-of-medicine"],"_links":{"self":[{"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/posts\/1304","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/comments?post=1304"}],"version-history":[{"count":7,"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/posts\/1304\/revisions"}],"predecessor-version":[{"id":1344,"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/posts\/1304\/revisions\/1344"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/media\/1307"}],"wp:attachment":[{"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/media?parent=1304"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/categories?post=1304"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.elsevierblogs.com\/virology\/wp-json\/wp\/v2\/tags?post=1304"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}