The role of diet on micro RNA and cancer prevention

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A balanced diet can effectively contribute to cancer prevention through its ability to control factors involved in cell disruption through micro RNA.

A scientific review conducted in Tokyo by the National Cancer Research Institute, together with the Division of Molecular and Cellular Medicine, reaches these conclusions. (1)

MicroRNA, a biomarker for early cancer detection

MicroRNA (or miRNA) is a recently discovered type of RNA that contributes to the regulation of an individual’s gene expression. An imbalance in its function appears to be a cause of promoting various diseases, including cancer. (2)

miRNA analysis represents a potential biomarker for early detection of cancer pathologies, even before they begin to develop at the affected site. Serum miRNA, in particular, seems the most promising for obtaining reliable information on the state of disease progression.

Cancer prevention, the three stages

Cancer prevention in epidemiology is distinguished into three forms, or stages, in relation to health status and possible disease development:

1) Primary prevention. The key to health is to implement preventive measures that aspire to avoid the occurrence of cancer and other diseases,

2) Secondary prevention. In the early stages of tumor development, action is taken with the aim of preventing the course and complete development of tumors,

3) Tertiary prevention. When the tumors are fully developed, the surgery aspires to prolong the patient’s life expectancy. (3)

Lifestyle, diet and miRNAs

Healthy and balanced lifestyle and diet are key factors in the primary prevention of serious and chronic diseases (NCDs, Non Communicable Diseases), as noted. Some nutrients and bioactive compounds, among others, have been shown to modulate miRNA concentration and function. And so to intervene in the gene expression underlying tumor initiation.

Dietary imbalances and unhealthy lifestyle habits conversely result in dysregulation of endogenous miRNAs, which can promote states of inflammation and predisposition to cancer, especially in combination with factors such as stress and aging.

Correction of daily habits and the intake of certain substances naturally contained in food are helpful in restoring proper miRNA expression.

Fig. 1. Relationship between health status and miRNA expression (Otsuka et al., 2021)

Diet and prevention

Polyphenols are the substances most involved in regulating the expression of various miRNAs imputed to control the development of different types of cancer, in addition to antioxidant activity, as noted. They can induce apoptosis in cancer cells, inhibit their proliferation or even metastasis by containing their spread to sites other than those of formation. Among the most important substances are:

quercetin. Known for its antioxidant properties, it is found in apples, onions, tomatoes, and green tea,

EGCG. Epigallocatechin-3-gallate is the most abundant polyphenol in green tea leaves,

curcumin. A characteristic ingredient in medicine as well as in Indian cuisine (now also in some dietary supplements), it is found in the turmeric rhizome,

genistein. Very present in legumes, especially in soybeans and lupins,

resveratrol. One of the most celebrated polyphenols because of its presence in red grapes that also resides in wine and because of its protective effects on the cardiovascular system, it also has chemopreventive action toward several types of cancer.

Metabolically derived products in turn play an important role in regulating the positive expression of miRNAs. Glucosinolates in broccoli, cauliflower and cabbage are converted to isothiocyanates, and among them sulforaphane and diindolylmethane are the most important in regulatory mechanisms. From the fermentation of insoluble fiber by the microbiota, butyrate is formed, which contributes to the performance of this function.

Current limits

The bioavailability of polyphenols and other natural substances is a limiting factor, since the positive regulatory action of micro RNA postulates their ability to reach the sites of interest at the right concentrations and in useful forms, without metabolic modifications that slow their effects or result in adverse effects.

Adverse effects of polyphenols have been verified, in some cases, in advanced stages of tumor development. Their use in the chemo- and radiotherapy treatment phases must therefore be carefully evaluated. Also taking into account the possible hormetic effect of polyphenols when brought in excessive concentrations. (4)

Interim conclusions

Micro RNAs are potential new biomarkers useful in detecting different types of cancer in the pre-development stages and adopting appropriate strategies to limit or prevent its actual development. A balanced and varied diet, rich in natural substances such as polyphenol phenolic compounds, is among the most beneficial strategies to achieve this.

Further studies e research is needed to understand in more detail the mechanisms underlying the natural substances in foods and the possibility of administering them in the most effective forms and doses to regulate miRNAs, which in turn require to be identified and characterized more precisely to improve the chances of implementing chemoprevention strategies. (5)

Dario Dongo and Andrea Adelmo Della Penna

Notes

(1) Otsuka et al. (2021) Possible connection between diet and microRNA in cancer scenario. Seminars in Cancer Biology 73:4-18, https://doi.org/10.1016/j.semcancer.2020.11.014

(2) MicroRNAs (miRNAs) are a class of noncoding RNAs that play important roles in regulating gene expression. Most miRNAs are transcribed from DNA sequences into primary miRNAs, then transformed into precursor miRNAs and finally into mature miRNAs. V. Jacob O’Brian et al. (2018). Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front. Endocrinol., 03 August 2018. https://doi.org/10.3389/fendo.2018.00402

(3) Lisa A. Kisling & Joe M. Das. (2021). Prevention strategies. StatPearls, 9.5.21, https://www.ncbi.nlm.nih.gov/books/NBK537222/

(4) Fernando et al. (2019). Dietary phytochemicals with anti-oxidant and pro-oxidant activities: A double-edged sword in relation to adjuvant chemotherapy and radiotherapy? Cancer Letters 452:168-177, https://doi.org/10.1016/j.canlet.2019.03.022

(5) However, the role of miRNAs as biomarkers needs to be further investigated with further research to better understand their primary prevention functions. Moreover, a single miRNA can affect multiple genes, and it is therefore necessary to identify an efficient and reliable identification system that can distinguish useful RNAs from potentially harmful ones

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Dario Dongo, lawyer and journalist, PhD in international food law, founder of WIISE (FARE - GIFT - Food Times) and Égalité.

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Graduated in Food Technologies and Biotechnologies, qualified food technologist, he follows the research and development area. With particular regard to European research projects (in Horizon 2020, PRIMA) where the FARE division of WIISE Srl, a benefit company, participates.