Characterization of circulating mirna expression profile in patients with cancer-associated cachexia

• Grant number: 24/17588-5
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: March 01, 2025
• End date: May 31, 2028
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Marilia Cerqueira Leite Seelaender
• Grantee: Giovana Parreira de Aquino
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cancer cachexia (CC) is a multifactorial syndrome characterized by weight loss with wasting of muscle tissue, with or without loss of fat mass. The common clinical manifestations are anorexia, chronic systemic inflammation, and catabolism, which can affect the quality of life/survival span and the tolerance of anti-cancer treatments, leading to cancer-related deaths. Currently, there are no highly specific biomarkers for this syndrome. Circulating levels of microRNAs (miRNAs), have been shown to be altered in cancer cachexia, as part of the complex cross-talk characteristic of cachexia. These small non-coding RNAs regulate gene expression post-transcriptionally and can be found within extracellular vesicles (EVs), specifically exosomes, which promote intertissue communication and stability when packaged. Several miRNAs have already been characterized in regard to their capacity of promoting alterations in muscle and adipose tissue, systemic inflammation, and interfering with metabolic pathways. However, the mechanism by which circulating miRNAs induce muscle and fat loss in cancer cachectic patients has not yet been established. Our goal is to characterize the miRNA expression profiles of liquid biopsies from patients with CC and non-cachectic cancer patients. With that purpose, we will firstly perform a meta-analysis, employing public databases, to identify differentially expressed circulating miRNAs in CC patients. Subsequently, we will quantify the expression profile of circulating miRNAs in both non-fractionated serum/plasma and exosomes isolated from CC patients and non-cachectic cancer patients. Additionally, exosomes obtained from primary culture of patient's tumour will be added to the ex-vivo culture of adipose and muscle tissue explants, as to analyze the in vitro pro-cachectic effects of specific exosomal miRNAs.