Examples of Inverse Comorbidity between Cancer and Neurodegenerative Diseases: A Possible Role for Noncoding RNA

Abstract

Cancer is one of the most common causes of death; in parallel, the incidence and prevalence of central nervous system diseases are equally high. Among neurodegenerative diseases, Alzheimer’s dementia is the most common, while Parkinson’s disease (PD) is the second most frequent neurodegenerative disease. There is a significant amount of evidence on the complex biological connection between cancer and neurodegeneration. Noncoding RNAs (ncRNAs) are defined as transcribed nucleotides that perform a variety of regulatory functions. The mechanisms by which ncRNAs exert their functions are numerous and involve every aspect of cellular life. The same ncRNA can act in multiple ways, leading to different outcomes; in fact, a single ncRNA can participate in the pathogenesis of more than one disease—even if these seem very different, as cancer and neurodegenerative disorders are. The ncRNA activates specific pathways leading to one or the other clinical phenotype, sometimes with obvious mechanisms of inverse comorbidity. We aimed to collect from the existing literature examples of inverse comorbidity in which ncRNAs seem to play a key role. We also investigated the example of mir-519a-3p, and one of its target genes Poly (ADP-ribose) polymerase 1, for the inverse comorbidity mechanism between some cancers and PD. We believe it is very important to study the inverse comorbidity relationship between cancer and neurodegenerative diseases because it will help us to better assess these two major areas of human disease.

Natural resistance to cancer: A window of hope

“…For example, TP53 is downregulated, while PIN1, WNT, and UPS are upregulated in cancer, as opposed to neurodegenerative diseases. 77 The enzyme PIN1 drives neuronal health by restoring amyloid precursor protein and phosphorylated tau protein to a functional conformation, while it serves as an oncogene in several cancer types. 78,79 In neurodegenerative disorders, PIN1 is downregulated or deficient in neural cells which leads to the aggregation and accumulation of β-amyloid and tau proteins, thereby promoting neurodegeneration.…”

Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System

“…The improvements in healthcare access and a concurrent rise in lifespan for the global population has resulted in an increased prevalence of neurodegenerative disorders [28,41,[73][74][75][76][77][78]. Diseases of the nervous system represent over six hundred disorders that lead to death and disability [61,76,77,79,80].…”

Targeting Orexin Receptors for the Treatment of Insomnia: From Physiological Mechanisms to Current Clinical Evidence and Recommendations

“…The complex interconnection between cancer, narcolepsy, and neurodegenerative diseases has recently been proposed as a possible case of orexin-dependent inverse comorbidity. 110 Orexin signaling has been linked to neuroinflammation in mouse models and to cancer in cell lines. 110 , 111 Moreover, the expression of the orexin-A receptor in various tumors, including colon, pancreas, and prostate cancers, and its ability to induce a proapoptotic activity in tumor cells, 112 suggested that orexin signaling through OX1R might have a promising therapeutic role also in cancer-related sleep disorders.…”