Decoding the role of inflammation-related microRNAs in cancer cachexia: a study using HPV16-transgenic mice and in silico approaches

• Type: Article in International Scientific Journal
• Date: 2022

Authors

Joana M. O. Santos (Author) Other; Sara Peixoto da Silva (Author) Other; Margarida M. S. M. Bastos (Author) FEUP; Paula A. Oliveira (Author) Other; Rui M. Gil da Costa (Author) Other; Rui Medeiros (Author) ICBAS

Journal

Title: Journal of Physiology and Biochemistry

Vol. 78

Pages: 439-455

ISSN: 1138-7548

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 3 Citations

Scopus - 3 Citations

Other information

Authenticus ID: P-00W-A15

DOI: 10.1007/s13105-021-00866-1

Abstract (EN): Cachexia is associated with poor prognosis in cancer patients, and inflammation is one of its main drive factors. MicroRNAs have recently emerged as important players in cancer cachexia and are involved in reciprocal regulation networks with pro-inflammatory signaling pathways. We hypothesize that inflammation-driven cancer cachexia is regulated by specific microRNAs. The aim of this study is to explore the expression and role of inflammation-related microRNAs in muscle wasting. HPV16-transgenic mice develop systemic inflammation and muscle wasting and are a model for cancer cachexia. We employed gastrocnemius muscle samples from these mice to study the expression of microRNAs. Bioinformatic tools were then used to explore their potential role in muscle wasting. Among the microRNAs studied, miR-223-3p (p = 0.004), let-7b-5p (p = 0.034), miR-21a-5p (p = 0.034), miR-150-5p (p = 0.027), and miR-155-5p (p = 0.011) were significantly upregulated in muscles from cachectic mice. In silico analysis showed that these microRNAs participate in several processes related to muscle wasting, including muscle structure development and regulation of the MAPK pathway. When analyzing protein- protein interactions (PPI)-networks, two major clusters and the top 10 hubs were obtained. From the top 10, Kras (p = 0.050) and Ccdn1 (p = 0.009) were downregulated in cachectic muscles, as well as Map2k3 (p = 0.007). These results show that miR-223-3p, let-7b-5p, miR-21a-5p, miR-150-5p, and miR-155-5p, play a role in muscle wasting in HPV16 transgenic mice, possible through regulating the MAPK cascades. Future experimental studies are required to validate our in silico analysis, and to explore the usefulness of these microRNAs and MAPK signaling as new potential biomarkers or therapy targets for cancer cachexia.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 17