miRNAs as biomarkers for early cancer detection and their application in the development of new diagnostic tools

Abstract

Over the last decades, microRNAs (miRNAs) have emerged as important molecules associated with the regulation of gene expression in humans and other organisms, expanding the strategies available to diagnose and handle several diseases. This paper presents a systematic review of literature of miRNAs related to cancer development and explores the main techniques used to quantify these molecules and their limitations as screening strategy. The bibliographic research was conducted using the online databases, PubMed, Google Scholar, Web of Science, and Science Direct searching the terms "microRNA detection", "miRNA detection", "miRNA and prostate cancer", "miRNA and cervical cancer", "miRNA and cervix cancer", "miRNA and breast cancer", and "miRNA and early cancer diagnosis". Along the systematic review over 26,000 published papers were reported, and 252 papers were returned after applying the inclusion and exclusion criteria, which were considered during this review. The aim of this study is to identify potential miRNAs related to cancer development that may be useful for early cancer diagnosis, notably in the breast, prostate, and cervical cancers. In addition, we suggest a preliminary top 20 miRNA panel according to their relevance during the respective cancer development. Considering the progressive number of new cancer cases every year worldwide, the development of new diagnostic tools is critical to refine the accuracy of screening tests, improving the life expectancy and allowing a better prognosis for the affected patients.

Keywords: Biomarkers; Breast cancer; Cervical cancer; Early cancer diagnosis; Liquid biopsies; MiRNA; Prostate cancer.

Fig. 1

MicroRNA expression and function on post-transcriptional regulation of mRNA. (1) Mature miRNAs are initially expressed in the nucleus in the pri-miRNAs form, which is cleaved by DGC58/Drosha proteins, resulting in the pre-miRNA form. (2) The intermediary pre-miRNA form is exported to the cytoplasm. (3) The intermediary pre-miRNA form interacts with Dicer, responsible for the final cleavage of the hairpin loop and result in a 20–25 nucleotide dsRNA structure. (4) Mature miRNAs are released and form the miR-RISC protein complex. (5) miR-RISC protein complex interacts with the complementary mRNA strand and the acts on post-transcriptional regulation mechanisms. (6) Mature miRNAs are released into exosome vesicles. (7) Mature miRNAs in exosomes can be detected in several biological fluids (as plasma, saliva, or urine)

Fig. 2

Representation in a Venn diagram of the sharing or differentially expressed miRNA profile in only one type, according to the proposed panels for (1) breast; (2) cervical; or (3) prostate cancer. The star represents the absence of over position on miRNA profile mutually altered in all three cancer types according to the literature reviewed. This possibility, however, was not excluded if we consider the expression of other miRNAs not presented in the tables

Fig. 3

Development of a low-cost platform to quantify miRNAs using minimally invasive samples and their application as a diagnostic tool for cancer screening. Among the desirable features for the application of a new diagnostic tool, this strategy may reduce the technical barriers to early cancer diagnosis and contribute to the application of miRNAs quantification as a powerful screening method. (1) Use of minimally invasive samples. (2) Few steps of sample processing until the complete miRNA isolation. (3) miRNA quantification and data analysis. (4) Clinical interpretation of results and effective communication of them between the health professional and the patient