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.

Keywords: cancer; inverse comorbidity; neurodegenerative diseases; noncoding RNAs.

Figure 1

General biological mechanisms leading to neurodegenerative disease or cancer.

Figure 2

Gene regulatory mechanism of ncRNA.

Figure 3

RNAs’ nomenclature and function. RNAs are classified based on their coding. Only two percent of RNAs code for proteins; most RNAs exert regulatory functions. lncRNA, long noncoding RNA; circular RNA; miRNA; microRNA; piRNA; piwi-interacting RNA; rasiRNA; repeat-associated small interfering RNA; scaRNA, small Cajal body-specific RNA; siRNA, small interfering RNA; snRNA, small nuclear RNA; snoRNA, small nucleolar RNA; tiRNA, transfer RNA; rRNA, stress-induced small RNA; tRNA, transfer RNA.

Figure 4

Examples of inverse comorbidity between tumors and Parkinson’s disease in which the miR-519a-3p and PARP1 gene play an important role. TGCTs, testicular germ cell tumors; HCC, hepatocellular carcinoma; GM, glioblastoma multiforme. Red arrow, upregulated; green arrow, downregulated.

Figure 5

miRNAs involved in inverse comorbidity mechanisms for the modulation of neurodegeneration, carcinogenesis and circadian genes.