Cancer-associated cachexia is a complex, heterogeneous, and multifactorial syndrome defined by dramatic alterations such as loss of appetite, metabolic variations, and body composition changes. The major feature of cachexia is represented by uncontrolled weight loss, resulting from the reduction of skeletal muscle and adipose tissue. Cachexia drastically impacts the quality of life of cancer patients, as they are less responsive to anti-cancer therapies and display poor prognosis: it has been estimated that nearly 20% of mortalities in cancer patients are attributed to the consequences of cachexia rather than to the tumor burden. Lean mass wasting is the result of enhanced proteolysis and impaired protein synthesis in skeletal muscle cells. The ubiquitin-proteasome pathway plays a crucial role in this imbalance, but it has been recently demonstrated that other factors are involved, like NF-kB signaling, calpains, and caspases.

Although the field has made great strides in understanding the processes regulating cancer cachexia, the complete picture of what is going on in this complex disorder has not been fully elucidated and novel contributing factors are still being discovered. There are no general guidelines for the treatment of cancer cachexia; however, several recent studies have immensely contributed to a better understanding of the mechanisms mediating the onset and progression of the disease. Many findings point out that microRNAs (miRNAs) play a crucial role in cancer cachexia. miRNAs are a group of regulatory non-coding RNAs whose mature form consists of ~19-22 nucleotides in length. miRNAs exert a well-recognized role in gene regulation, usually at the post-translational level, and play a central role in different biological processes including cell differentiation, chromatin remodeling, and development, and are usually dysregulated in many types of cancer. Moreover, miRNAs are broadly studied as biomarkers at both diagnostic and prognostic level as well as indicators of response to treatments. miRNAs can also be secreted by cancer cells: the so-called “circulating miRNAs” which are detected in plasma, serum, milk, urine, or saliva and act as biologically active molecules. They can be uptaken by cells surrounding the tumor, hence modulating gene expression and the response of the tumor microenvironment.

In skeletal muscle, miRNAs can induce muscle hypertrophy and regulate the skeletal muscle size, regulate myogenesis, inhibit the expression of proteins associated with muscle protein synthesis, or impair signaling pathways involved in such processes, hence promoting muscle atrophy and exacerbating myopenia. Moreover, several circulating miRNAs regulate muscle wasting and their expression was found to correlate with pro-inflammatory cytokine levels or with myopenia in cancer patients through the promotion of cell death in myoblasts.

This Research Topic will explore and discuss the potential role of miRNAs in diagnosis, prognosis, and therapy as well as in the regulation of the molecular and cellular processes that mediate the onset and progression of the cachexia syndrome.

We welcome the submission of Original Research, Reviews, Mini-Reviews, Perspectives, and Opinions covering, but not limited to, the following topics:

• miRNA modulation of muscle atrophy.
• The role of circulating miRNAs in cancer cachexia.
• miRNA-mediated regulation of the inflammatory response pathways.
• The role of miRNAs in the cross-talk at the tumor microenvironment level in the cachexia syndrome.

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Frontiers in Genetics

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