{"540761":{"#nid":"540761","#data":{"type":"news","title":"Restoring Chemotherapy Sensitivity by Boosting MicroRNA Levels","body":[{"value":"\u003Cp\u003EBy increasing the level of a specific microRNA (miRNA) molecule, researchers have for the first time restored chemotherapy sensitivity in vitro to a line of human pancreatic cancer cells that had developed resistance to a common treatment drug.\u003C\/p\u003E\u003Cp\u003EIf the miRNA molecules can be delivered to cells in the human body \u2013 potentially with nanoparticles \u2013 the technique might one day be used to battle the chemotherapy resistance that often develops during cancer treatment. A research team at the Georgia Institute of Technology identified the miRNA used in the research with a computer algorithm that compared the ability of different miRNAs to control the more than 500 genes that were up-regulated in drug-resistant cancer cells.\u003C\/p\u003E\u003Cp\u003EThe study was reported May 27 in the Nature Publishing Group journal \u003Cem\u003ECancer Gene Therapy\u003C\/em\u003E.\u003C\/p\u003E\u003Cp\u003E\u201cWe were specifically interested in what role miRNAs might play in developing drug resistance in these cancer cells,\u201d said \u003Ca href=\u0022http:\/\/www.biology.gatech.edu\/people\/john-mcdonald\u0022\u003EJohn McDonald\u003C\/a\u003E, a professor in Georgia Tech\u2019s \u003Ca href=\u0022http:\/\/www.biology.gatech.edu\/\u0022\u003ESchool of Biology\u003C\/a\u003E and director of its Integrated Cancer Research Center. \u201cBy increasing the levels of the miRNA governing the suite of genes we identified, we increased the cells\u2019 drug sensitivity back to what the baseline had been, essentially undoing the resistance. This would suggest that for patients developing chemotherapy resistance, we might one day be able to use miRNAs to restore the sensitivity of the cancer cells to the drugs.\u201d\u003C\/p\u003E\u003Cp\u003EMicroRNAs are small non-coding molecules that function in RNA silencing and post-transcriptional regulation of gene expression. The miRNAs operate via base-pairing with complementary sequences within messenger RNA (mRNA) molecules, silencing the mRNA molecules that control the expression of certain proteins.\u003C\/p\u003E\u003Cp\u003ERoman Mezencev, a senior research scientist in the McDonald lab, began by exposing a line of pancreatic cancer cells (BxPC3) to increasing levels of the chemotherapy drug cisplatin. After each in vitro treatment, surviving cells were allowed to proliferate before being exposed to a higher level of the drug. After approximately a year and 20 treatment cycles, the resulting cell line had a resistance to cisplatin that was 15 times greater than that of the original cancer cells.\u003C\/p\u003E\u003Cp\u003EThe next step was to study the genetic changes associated with the resistance, comparing levels of more than 2,000 miRNAs in the cisplatin-resistant line to the original cell line that had not been exposed to the drug. Using a hidden Markov model (HMM) algorithm, they found 57 miRNAs that were either up-regulated or down-regulated, and identified miR-374b as the molecule most likely to be controlling the genes that govern chemotherapy resistance.\u003C\/p\u003E\u003Cp\u003EWhile previous work by other researchers has shown that miRNAs can provide a mechanism for the development of drug resistance, the Georgia Tech team took the findings a step farther by increasing the expression of miR-374b. When they did, they found that the cells previously resistant to the cisplatin were again sensitive to the drug \u2013 almost back to their original levels.\u003C\/p\u003E\u003Cp\u003ETechniques to control protein expression are already being used in cancer therapy, but McDonald believes there may be benefits in targeting the activity higher up in the process \u2013 at the RNA level. Studies by the Georgia Tech team and by other researchers clearly show an association between chemotherapy resistance and changes in levels of certain miRNAs.\u003C\/p\u003E\u003Cp\u003E\u201cMolecular evolution is a highly efficient process,\u201d McDonald said. \u201cOur evidence suggests that many of the genes regulated by a single microRNA are involved in coordinated cellular functions \u2013 in this case, drug resistance. We believe that microRNAs might be particularly good cancer therapeutic agents because when we manipulate them, we are manipulating suites of functionally coordinated genes.\u201d\u003C\/p\u003E\u003Cp\u003EA next step will be to study the effects of manipulating miRNA levels in animal cancer models. The McDonald research team is currently pursuing this possibility by inserting the microRNAs into tumors using nanoscale hydrogels developed by Andrew Lyon, former chair of Georgia Tech\u2019s School of Chemistry and Biochemistry.\u003C\/p\u003E\u003Cp\u003EMcDonald says the study confirms the role of miR-374b in creating resistance, though he says there could be other microRNA molecules involved, as well.\u003C\/p\u003E\u003Cp\u003E\u201cThese cells have acquired resistance to the drug, and we have found a microRNA that seems to be playing a major role,\u201d he said. \u201cWe have shown that we can bring sensitivity to drugs back by restoring levels of miR374b, but there may be other miRNAs that will work equally as well. Just as there are multiple pathways to establish cancer and chemoresistance, there may be multiple pathways to restore chemosensitivity, as well.\u201d\u003C\/p\u003E\u003Cp\u003EIf cancer could one day be treated using miRNAs, it\u2019s likely to be a continuing battle rather than a decisive victory, McDonald said. Cancer cells are very resourceful, and will likely find a new genetic route to resistance if one pathway is destroyed. That could require use of a different miRNA to reverse resistance.\u003C\/p\u003E\u003Cp\u003EWhile the miRNA research isn\u2019t likely to provide a \u201cmagic bullet\u201d for cancer, it does show the possible role of these tiny RNA molecules in controlling a broad class of bodily processes.\u003C\/p\u003E\u003Cp\u003E\u201cThere is growing evidence that this class of small regulatory RNAs may be involved in many processes ranging from evolution to heart disease,\u201d he said. \u201cMiRNAs are emerging as important players in cancer in general. Here, we are focusing on just one particular aspect of it.\u201d\u003C\/p\u003E\u003Cp\u003EIn addition to those already mentioned, the research team included R. Schreiber and L.V. Matyunina, both from Georgia Tech. In addition Schreiber is affiliated with the Faculdade de Ci\u00eancias M\u00e9dicas \u2013 UNICAMP in Brazil. The work was supported by funds from the Deborah Nash Endowment and the Mark Light Fellowship.\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ECITATION\u003C\/strong\u003E: R. Schreiber, et al., \u201cEvidence for the role of microRNA 374b in acquired cisplatin resistance in pancreatic cancer cells,\u201d (Cancer Gene Therapy, 2016). \u003Ca href=\u0022http:\/\/dx.doi.org\/10.1038\/cgt.2016.23\u0022\u003Ehttp:\/\/dx.doi.org\/10.1038\/cgt.2016.23\u003C\/a\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EResearch News\u003C\/strong\u003E\u003Cbr \/\u003E\u003Cstrong\u003EGeorgia Institute of Technology\u003C\/strong\u003E\u003Cbr \/\u003E\u003Cstrong\u003E177 North Avenue\u003C\/strong\u003E\u003Cbr \/\u003E\u003Cstrong\u003EAtlanta, Georgia 30332-0181 USA\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EMedia Relations Contacts\u003C\/strong\u003E: John Toon (404-894-6986) (\u003Ca href=\u0022mailto:jtoon@gatech.edu\u0022\u003Ejtoon@gatech.edu\u003C\/a\u003E) or Ben Brumfield (404-385-1933) (\u003Ca href=\u0022mailto:ben.brumfield@comm.gatech.edu\u0022\u003Eben.brumfield@comm.gatech.edu\u003C\/a\u003E).\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EWriter\u003C\/strong\u003E: John Toon\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EBy increasing the level of a specific microRNA (miRNA) molecule, researchers have for the first time restored chemotherapy sensitivity in vitro to a line of human pancreatic cancer cells that had developed resistance to a common treatment drug.\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Researchers have restored chemotherapy sensitivity in vitro to a line of human pancreatic cancer cells that had developed resistance."}],"uid":"27303","created_gmt":"2016-05-26 22:18:01","changed_gmt":"2016-10-08 03:21:49","author":"John Toon","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2016-05-27T00:00:00-04:00","iso_date":"2016-05-27T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"540721":{"id":"540721","type":"image","title":"Pancreatic cancer cells and microRNA","body":null,"created":"1464710400","gmt_created":"2016-05-31 16:00:00","changed":"1475895329","gmt_changed":"2016-10-08 02:55:29","alt":"Pancreatic cancer cells and microRNA","file":{"fid":"89615","name":"microrna-resistance_3468.jpg","image_path":"\/sites\/default\/files\/images\/microrna-resistance_3468.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/microrna-resistance_3468.jpg","mime":"image\/jpeg","size":1306527,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/microrna-resistance_3468.jpg?itok=8yVcxtI0"}},"540731":{"id":"540731","type":"image","title":"Pancreatic cancer cells and microRNA2","body":null,"created":"1464710400","gmt_created":"2016-05-31 16:00:00","changed":"1475895329","gmt_changed":"2016-10-08 02:55:29","alt":"Pancreatic cancer cells and microRNA2","file":{"fid":"89616","name":"microrna-resistance_3463.jpg","image_path":"\/sites\/default\/files\/images\/microrna-resistance_3463.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/microrna-resistance_3463.jpg","mime":"image\/jpeg","size":1207681,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/microrna-resistance_3463.jpg?itok=QQfwqe-K"}},"540751":{"id":"540751","type":"image","title":"Pancreatic cancer cells and microRNA3","body":null,"created":"1464710400","gmt_created":"2016-05-31 16:00:00","changed":"1475895331","gmt_changed":"2016-10-08 02:55:31","alt":"Pancreatic cancer cells and microRNA3","file":{"fid":"89618","name":"microrna-resistance_3475.jpg","image_path":"\/sites\/default\/files\/images\/microrna-resistance_3475.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/microrna-resistance_3475.jpg","mime":"image\/jpeg","size":1141899,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/microrna-resistance_3475.jpg?itok=W-yGCOqg"}}},"media_ids":["540721","540731","540751"],"groups":[{"id":"1188","name":"Research Horizons"}],"categories":[{"id":"140","name":"Cancer Research"},{"id":"146","name":"Life Sciences and Biology"},{"id":"135","name":"Research"}],"keywords":[{"id":"385","name":"cancer"},{"id":"1562","name":"Cancer Cells"},{"id":"1439","name":"chemotherapy"},{"id":"172088","name":"chemotherapy resistance"},{"id":"2371","name":"John McDonald"},{"id":"170335","name":"microRNA"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"},{"id":"39431","name":"Data Engineering and Science"}],"news_room_topics":[{"id":"71891","name":"Health and Medicine"}],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003EJohn Toon\u003C\/p\u003E\u003Cp\u003EResearch News\u003C\/p\u003E\u003Cp\u003E\u003Ca href=\u0022mailto:jtoon@gatech.edu\u0022\u003Ejtoon@gatech.edu\u003C\/a\u003E\u003C\/p\u003E\u003Cp\u003E(404) 894-6986\u003C\/p\u003E","format":"limited_html"}],"email":["jtoon@gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}