Show simple item record

dc.contributor.authorMcGregor, Robin A.
dc.date.accessioned2010-11-23T16:24:20Z
dc.date.available2010-11-23T16:24:20Z
dc.date.issued2009-09
dc.identifier.urihttp://hdl.handle.net/10399/2308
dc.description.abstractMicroRNAs are powerful post-transcriptional regulators of gene expression and are biomarkers of chronic diseases such as cancer. This thesis explores the role of microRNAs in human cancer cachexia and Type 2 diabetes. MicroRNA expression was measured in skeletal muscle biopsies using RT-qPCR. In pancreatic cancer cachexia patients, expression of microRNA-1, microRNA-133a, microRNA-133b and microRNA-206 was negatively related to weight loss. In Type 2 diabetes skeletal muscle, microRNA-133a and microRNA-206 expression was down-regulated, but there was no evidence of altered microRNA transcription or processing and target expression was unchanged. Importantly, microRNA-133a expression predicted fasting glucose, glucose tolerance and insulin resistance, and therefore may be a biomarker of Type 2 diabetes. Experimental validation of microRNA arrays was unsuccessful in identifying further novel cancer cachexia and Type 2 diabetes microRNA biomarkers. MicroRNA knockdown validated CDC42 and PTBP1 as microRNA-133a targets in myoblasts. In addition, muscle microRNA expression may be regulated by insulin and TNFa. In conclusion, microRNA-133a may be a skeletal muscle biomarker of Type 2 diabetes and cancer cachexia, microRNA-133a responds to extracellular insulin and TNFa, but it remains to be established whether microRNA-133a contributes to cancer cachexia or Type 2 diabetes pathogenesis.en_US
dc.language.isoenen_US
dc.publisherHeriot-Watt Universityen_US
dc.publisherEngineering and Physical Sciencesen_US
dc.rightsAll items in ROS are protected by the Creative Commons copyright license (http://creativecommons.org/licenses/by-nc-nd/2.5/scotland/), with some rights reserved.
dc.titleSkeletal muscle microRNA's in human cancer cachexia and type 2 diabetesen_US
dc.typeThesisen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record