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The role of diet on micro RNA and cancer prevention

A balanced diet can effectively contribute to the prevention of tumors thanks to the ability to control the factors involved in the alteration of cells through micro RNA.

These conclusions are reached by the scientific review conducted in Tokyo by the National Institute for Cancer Research, together with the Division of Molecular and Cellular Medicine. (1)

MicroRNA, a biomarker for early cancer detection

The microRNA (or miRNA) is a recently discovered type of RNA that contributes to the regulation of the expression of an individual's genes. An imbalance in its functionality seems to be the cause of promoting various diseases, including cancer. (2)

The analysis of miRNA represents a potential biomarker for the early detection of tumor pathologies, even before they begin to develop in the affected site. Serum miRNA, in particular, appears to be the most promising for obtaining reliable information on the progress of the disease.

Cancer prevention, the three stages

Cancer prevention in epidemiology it is divided into three forms, or stages, in relation to the state of health and the possible development of diseases:

1) Primary prevention. The key to health consists in the implementation of preventive measures that aim to avoid the manifestation of cancer and other diseases,

2) Secondary prevention. In the early stages of cancer development, action is taken in order to avoid their course and complete development,

3) Tertiary prevention. When the tumors are fully developed, the intervention aims to prolong the patient's life expectancy. (3)

Lifestyle, diet and miRNA

Lifestyle and diet healthy and balanced are key factors in the primary prevention of severe and chronic diseases (NCDs, Non-Communicable Diseases), as seen. Among other things, some nutrients and bioactive compounds have been shown to modulate the concentration and functioning of miRNAs. And so to intervene in the gene expression at the basis of tumor initiation.

Food imbalances and unhealthy lifestyle habits, on the other hand, lead to a dysregulation of endogenous miRNAs, which can promote states of inflammation and predisposition to tumors, especially in combination with factors such as stress and aging.

Correction of habits daily and the intake of some substances naturally contained in food are useful in restoring the correct expression of miRNAs.

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 the various miRNAs attributed to the control of the development of different types of cancer, in addition to the antioxidant activity, as seen. They can induce apoptosis in cancer cells, inhibit their proliferation or even metastasis, limiting their spread to sites other than those of formation. The most important substances include:

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

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

- curcumin. Characteristic ingredient of medicine, as well as of Indian cuisine (now also in some food supplements), it is present in the rhizome of turmeric,

- genistein. Very present in legumes, especially in soy and lupins,

resveratrol. One of the most famous polyphenols, due to its presence in red grapes which also remains in wine and for its protective effects on the cardiovascular system, also carries out a chemopreventive action against various types of cancer.

The products of metabolic derivation in turn they play an important role in regulating the positive expression of miRNAs. The glucosinolates contained in broccoli, cauliflower and cabbage are converted into isothiocyanates and among these sulforaphane and diindolylmethane are the most important in the regulatory mechanisms. From the fermentation of the insoluble fiber by the microbiota butyrate is formed, which contributes to the performance of this functionality.

Current limits

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

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

Provisional conclusions

The micro RNAs they are new potentials biomarkers useful in identifying different types of cancer in the pre-development stages and adopting appropriate strategies to limit or avoid their actual development. A balanced and varied diet, rich in natural substances such as phenolic compounds polyphenols, is one of the most advantageous strategies to achieve this result.

Further studies and research is needed to understand in more detail the mechanisms underlying the natural substances present 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 in a more precise to improve the possibilities of implementing chemoprevention strategies. (5)

Dario Dongo and Andrea Adelmo Della Penna

Footnotes

(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 non-coding 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) The role of miRNAs such as biomarker however, it must be investigated with further research to better understand their primary prevention functions. Furthermore, a single miRNA can concern multiple genes and it is therefore necessary to identify an efficient and reliable identification system, able to 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.

Andrea Adelmo Della Penna
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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.

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