PXD028554-1

PXD028554 is an original dataset announced via ProteomeXchange.

Title	Mechanisms associated with systemic effects of cancer
Description	Cancer is considered as a disease of a specific organ, but its effects are felt throughout the body. The systemic effects of cancer can lead to weakness in muscles and heart, which hastens cancer-associated death. miR-486 is a myogenic microRNA and its reduced expression in skeletal muscle is observed in muscular dystrophy. Muscle-specific transgenic expression of miR-486 using muscle creatine kinase promoter (MCK-miR-486) partially rescues skeletal muscle defects in muscular dystrophy animal models. We had previously demonstrated reduced circulating and skeletal muscle levels of miR-486 in several cancer types and lower miR-486 levels correlated with skeletal muscle defects and functional limitations in mammary tumor models. Therefore, skeletal muscle defects induced by cancer could resemble defects observed in various dystrophies, which could be reversed through skeletal muscle expression of miR-486. We performed functional limitations studies and biochemical analysis of skeletal muscles of MMTV-Neu transgenic mice that mimic HER2+ breast cancer and MMTV-PyMT transgenic mice that mimic luminal subtype B breast cancer and these mice crossed to MCK-miR-486 transgenic mice. miR-486 significantly prevented tumor-induced reduction in muscle contraction force, grip strength, and rotarod performance in MMTV-Neu, but not in MMTV-PyMT mice. In MMTV-Neu model, miR-486 reversed several of the cancer-induced changes in skeletal muscle including loss of p53, phospho-AKT, and phospho-laminin alpha 2 (LAMA2) and gain of phosphorylation of the pre-mRNA processing factor hnRNPA0 and the splicing factor SRSF10. LAMA2 is a part of the dystrophin-associated glycoprotein complex, and its loss-of-function mutation is associated with congenital muscular dystrophy. Thus, similar to muscular dystrophy, miR-486 has the potential to reverse skeletal muscle defects and cancer burden in select cancer types.
HostingRepository	PRIDE
AnnounceDate	2022-05-19
AnnouncementXML	Submission_2022-05-19_12:34:18.100.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD028554
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Emma Doud
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-16 07:39:39	ID requested
⏵ 1	2022-05-19 12:34:18	announced

Wang R, Kumar B, Doud EH, Mosley AL, Alexander MS, Kunkel LM, Nakshatri H, Skeletal muscle-specific overexpression of miR-486 limits mammary tumor-induced skeletal muscle functional limitations. Mol Ther Nucleic Acids, 28():231-248(2022) [pubmed]

submitter keyword: Mouse, skeletal muscle, breast cancer, functional limitations, miR-486, LC-MSMS

Harikrishna Nakshatri, BVSc., PhD
contact affiliation	Professor of Surgery Marian J. Morrison Chair in Breast Cancer Research Associate Director of Education, IU Simon Cancer Center Co-Director, IU Simon Cancer Center Breast Cancer Program Department of Surgery, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA Richard L Roudebush VA Medical Center, Indianapolis, IN 46202, USA C218C, 980 West Walnut St. Indianapolis, IN 46202, USA 317 278 2238
contact email	hnakshat@iupui.edu
lab head
Emma Doud
contact affiliation	Indiana University School of Medicine
contact email	edoud@iu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028554
     1. Label: PRIDE project
     2. Name: Mechanisms associated with systemic effects of cancer