The Impact of Oxidoreductases-Related MicroRNAs in Glucose Metabolism of Renal Cell Carcinoma and Prostate Cancer

The reprogramming of metabolism is one of cancer hallmarks. Glucose’s metabolism, as one of the main fuels of cancer cells, has been the focus of several research studies in the oncology field. However, because cancer is a heterogeneous disease, the disruptions in glucose metabolism are highly variable depending of the cancer. In fact, Renal Cell Carcinoma (RCC) and Prostate Cancer (PCa), the most lethal and common urological neoplasia, respectively, show different disruptions in the main pathways of glucose catabolism: glycolysis, lactate fermentation and Krebs Cycle. Oxidoreductases are a class of enzymes that catalyze electrons transfer from one molecule to another and are present in these three pathways, posing as an opportunity to better understand these catabolic deregulations. Furthermore, nowadays it is recognized that their expression is modulated by microRNAs (miRNAs), in this book chapter, we selected the known miRNAs that directly target these oxidoreductases and analyzed their deregulation in both cancers. The characterization of these miRNAs opens a new door that could be applied in patients’ stratification and therapy monitorization because of their potential as cancer biomarkers. Additionally, their delivery to cancer cells, using glucose capped NPs could help establish new therapeutic strategies that would improve RCC and PCa management.

Steroidal 5α-Reductase: A Therapeutic Target for Prostate Disorders

Steroidal 5α-reductase is a system of NADPH dependent enzyme that catalyzes the irreversible conversion of Δ4–3-ketosteroid precursor (testosterone) to its corresponding 5α-reduced metabolite (dihydrotestosterone). Initial role of DHT was discovered through males pseudohermaphroditism, a genetic disorder with complete or partial 5α-reductase deficiency accompanied with features at critical juncture of fetal and postnatal development. However, excessive DHT production, has brought a revolution in revealing the etiology of complications like prostate cancer and benign prostatic hyperplasia. Over the last two decades, converging lines of evidences have highlighted the role of 5α-reductase inhibitors in the treatment of these androgen dependent disorders. Finasteride and Dutasteride, are the two clinically approved inhibitors available in the market, that helps in reducing the prostate volume by blocking the 5a-reductase enzyme.

Monoamine Oxidase A (MAO-A): A Therapeutic Target in Lung Cancer

Monoamine oxidase-A (MAO-A), a pro-oxidative enzyme catalyzes the oxidative deamination of endogenous and exogenous monoamines/neurotransmitters like dopamine, serotonin, norepinephrine or tyramine and converting them into their corresponding aldehydes and reactive oxygen species (ROS). Hyperactivity of MAO-A has been shown to be involved in depression, neuro-degeneration including Parkinson’s and Alzheimer’s diseases, neuropsychiatric disorders and cardiovascular diseases. Our recent results however demonstrated the involvement of MAO-A in promoting aggressiveness of lung carcinoma. We found both constitutive and inducible expression of MAO-A in non-small cell lung cancer cells H1299 and in A549 lung epithelial carcinoma cells. By using knockout (by CRISPR-Cas9 gene editing technology) or knockdown (using MAO-A specific esiRNA) MAO-A cells we demonstrated the role of MAO-A in promoting lung cancer aggressiveness and epithelial to mesenchymal transition (EMT). From our observations, we can conclude that MAO-A may be considered as a potential therapeutic target for the intervention and treatment of lung carcinoma.

Neurodegeneration: Diagnosis, Prevention, and Therapy

Neurodegenerative disorders (NDDs) are a broad range of pathological conditions which target the neurons, creating problems in movements and mental functions. The NDDs have drawn a lot of attention among the diseases because of its complexity in causes and symptoms, lack of proper effective treatment(s), no report of irreversibility, and poor impact on social and financial aspects. Individual’s vulnerability towards the stress-related biochemical alterations including increase in oxidase enzymes’ activities and generation of free radicals, abnormal protein dynamics, mitochondrial dysfunctions, and neuroinflammation often lead to degeneration of neuronal cells. Some advanced techniques are now able to detect the development and progression of different NDDs’ complications. The current focus of research on NDDs is to establish convenient therapeutic strategies by targeting different aspects including upliftment of cellular defense mechanisms, especially oxidoreductases as a protective tool. This chapter focused on those updated information on the development, diagnosis, prevention, and therapeutic strategies of NDDs.