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DTSTAMP:20260526T130035Z
DESCRIPTION:\n	Dr. Imed Gallouzi - Department of Biochemistry\n\nThe role of
  RNA Binding proteins in the onset of cancer-induced cachexia: new potenti
 al avenue for therapy\n\nPro-inflammatory diseases\, such as cancer\, AIDS
 \, and COPD\, are often associated with a progressive loss of skeletal mus
 cle tissue\, a syndrome also known as cachexia. It is known that pro-infla
 mmatory cytokines\, such as TNFa and IFNg\, trigger muscle loss by activat
 ing downstream inflammatory pathways. In this seminar I will present evide
 nce supporting the idea that RNA binding proteins\, such as HuR and the mR
 NA decay factor KSRP play a key role in the onset of this deadly syndrome.
  Under cachectic conditions\, HuR switches its function from a promoter of
  muscle fiber formation to become an inducer of muscle loss. HuR binds to 
 the STAT3 mRNA\, which encodes one of the main effectors of this condition
 \, promoting its expression both in vitro and in vivo. While HuR does not 
 affect the stability and the cellular movement of this transcript\, HuR pr
 omotes the translation of the STAT3 mRNA by preventing miR-330-mediated tr
 anslation inhibition. To achieve this effect\, HuR directly binds to a U-r
 ich element in the STAT3 mRNA-3’untranslated region (UTR) located within t
 he vicinity of the miR-330 seed element. We next investigated the in vivo 
 role of HuR in muscle physiology and disease-induced atrophy. We observed 
 that that muscle-specific HuR knockout (muHuR-KO) mice have high exercise 
 endurance that is associated with enhanced oxygen consumption and carbon d
 ioxide production. muHuR-KO mice exhibit a significant increase in the pro
 portion of oxidative type I fibers in several skeletal muscles. HuR mediat
 es these effects by collaborating with the mRNA decay factor KSRP to desta
 bilize the PGC-1α mRNA. The type I fiber-enriched phenotype of muHuR-KO mi
 ce protects against cancer cachexia-induced muscle loss. Therefore\, our s
 tudies demonstrate the role of HuR in the onset of cancer-induced muscle w
 asting and provide a proof-of-principle that HuR expression can be targete
 d therapeutically in skeletal muscles to combat this deadly condition.\n
DTSTART:20191002T153000Z
DTEND:20191002T163000Z
LOCATION:Room 1/12\, Strathcona Anatomy and Dentistry Building\, CA\, QC\, 
 Montreal\, H3A 0C7\, 3640 rue University
SUMMARY:Departmental Seminar: Imed Gallouzi
URL:https://www.mcgill.ca/anatomy/channels/event/departmental-seminar-imed-
 gallouzi-300462
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