The pathway to cancer Cachexia: Microrna-regulated networks in muscle wasting based on integrative meta-analysis
Abstract
Cancer cachexia is a multifactorial syndrome that leads to significant weight loss. Cachexia affects 50%-80% of cancer patients, depending on the tumor type, and is associated with 20%-40% of cancer patient deaths. Besides the efforts to identify molecular mechanisms of skeletal muscle atrophy—a key feature in cancer cachexia—no effective therapy for the syndrome is currently available. MicroRNAs are regulators of gene expression, with therapeutic potential in several muscle wasting disorders. We performed a meta-analysis of previously published gene expression data to reveal new potential microRNA-mRNA networks associated with muscle atrophy in cancer cachexia. We retrieved 52 differentially expressed genes in nine studies of muscle tissue from patients and rodent models of cancer cachexia. Next, we predicted microRNAs targeting these differentially expressed genes. We also include global microRNA expression data surveyed in atrophying skeletal muscles from previous studies as background information. We identified deregulated genes involved in the regulation of apoptosis, muscle hypertrophy, catabolism, and acute phase response. We further predicted new microRNA-mRNA interactions, such as miR-27a/Foxo1, miR-27a/Mef2c, miR-27b/Cxcl12, miR-27b/Mef2c, miR-140/Cxcl12, miR-199a/Cav1, and miR-199a/Junb, which may contribute to muscle wasting in cancer cachexia. Finally, we found drugs targeting MSTN,CXCL12, and CAMK2B, which may be considered for the development of novel therapeutic strategies for cancer cachexia. Our study has broadened the knowledge of microRNA-regulated networks that are likely associated with muscle atrophy in cancer cachexia, pointing to their involvement as potential targets for novel therapeutic strategies.
How to cite this document
Language
Sponsor
Grant number
Collections

Related items
Showing items related by title, author, creator and subject.
-
Núcleos de Ensino da Unesp: artigos 2009
Pinho, Sheila Zambello de; Oliveira, José Brás Barreto de
; Gazola, Rodrigo José Cristiano
; Mazotti, Adriano César
; Molero, Camila Schimite
; Mendes, Carolina Borghi
; Mello, Denise Fernandes de
; Marques, Emilia de Mendonça Rosa
; Talamoni, Jandira Liria Biscalquini
; Silva, José Humberto Dias da
et al. (Coleção PROGRAD (UNESP), 2011) [Livro]
-
Núcleos de Ensino da Unesp: artigos 2008
Pinho, Sheila Zambello de; Oliveira, José Brás Barreto de
; Pontes, Sueli Rodrigues
; Almeida, Djanira Soares de Oliveira e
; Godoy, Kathya Maria Ayres de
; Rosa, Claudia de Souza
; Nunes, Julianus Araújo
; Salvador, Sérgio Azevedo
; David, Célia Maria
; Vilche Peña, Angel Fidel
et al. (Coleção PROGRAD (UNESP), 2011) [Livro]
-
Ser e tornar-se professor: práticas educativas no contexto escolar
Pinho, Sheila Zambello de; Spazziani, Maria de Lourdes
; Mendonça, Sueli Guadelupe de Lima
; Rubo, Elisabete Aparecida Andrello
; Villarreal, Dalva Maria de Oliveira
; Duarte, Camila
; Okamoto, Mary Yoko
; Souza, Thais R.
; Garms, Gilza Maria Zauhy
; Marin, Fátima Aparecida Dias Gomes
et al. (Coleção PROGRAD (UNESP), 2012) [Livro]