Scholarship 23/15976-5 - Atrofia muscular, Neoplasias - BV FAPESP
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Long Non-Coding RNAs in Cancer Cell Secretome: A Comprehensive Analysis of Their Role in Muscle Atrophy in Cancer Associated Cachexia

Grant number: 23/15976-5
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Start date until: May 01, 2024
End date until: April 30, 2025
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Robson Francisco Carvalho
Grantee:Amanda Piveta Schnepper
Supervisor: Rory Johnson
Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Institution abroad: University College Dublin, Ireland  
Associated to the scholarship:22/06775-3 - Functional prediction of long non-coding RNAs using transcriptome data in cancer-associated cachexia, BP.DR

Abstract

Cancer-associated cachexia is a debilitating syndrome characterized by weight loss and muscle wasting, profoundly affecting patients' quality of life and prognosis. The prevalence of cachexia among cancer patients is estimated to range from 15% to 70%, with variations depending on the specific tumor type. The syndrome significantly compromises the response to radiotherapy and chemotherapy and is characterized by physiological, metabolic, and immunological imbalances that disrupt energy and protein levels. Cancer cachexia remains underdiagnosed and without approved treatments. To date, there has been no successful development of a therapy for cancer cachexia. The tumor microenvironment secretome (TME) plays a crucial role in cancer development and can trigger cachexia development. Various pro-inflammatory cytokines secreted by the tumor in skeletal muscle can mediate muscle wasting. However, identifying muscle atrophy mediators secreted by the tumor remains challenging and underexplored. Long non-coding RNAs (lncRNAs) are RNA molecules longer than 200 nt that do not code for proteins. lncRNAs play an important role at different levels of cellular regulation. In cancer, it is known that lncRNAs influence tumor cell proliferation and impact patient prognosis. LncRNAs have gained significant attention as a promising candidate in cancer diagnosis, prognosis, and therapy. They are being examined as therapeutic targets in clinical trials for various malignancies. In cancer-associated cachexia, few studies correlate the role of lncRNAs in muscle atrophy, and little is known about the impact of lncRNAs on the secretome of cachexia-mediating molecules. Therefore, our objective is to identify, characterize, and predict the function of lncRNAs associated with protein secretion pathways in various tumors. This characterization will be carried out through the analysis of scRNA-seq data from 12 tumor types available in public databases, construction of lncRNA-mRNA co-expression networks using Seurat and SCENIC, and functional assays to understand the role of lncRNAs in muscle atrophy. In this way, we hope to elucidate interaction pathways of molecular factors underlying cancer cachexia and explore possible therapeutic strategies.

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