Background

Over the last decades, microRNAs (miRNAs) have emerged as important molecules associated with regulation of gene expression in humans and other organisms, expanding the strategies available to diagnose and handle several diseases. Briefly, miRNAs are small non-coding RNAs (21–25 nucleotides) and derived from coding and non-coding transcription units in genic (intronic or exonic) and intergenic regions [1, 2].

These molecules were initially described in nematodes and implicated in the regulation of genic expression by post-transcriptional mechanisms targeting complementary mRNAs and affecting several biological processes, as cell signaling, differentiation, proliferation, and activation/inhibition of apoptotic mechanisms [2,3,4]. Currently, over 38 thousand miRNAs sequences from 271 species were described and cataloged on the miRBase (http://www.mirbase.org), which 1917 sequences are from Homo sapiens and may represent an important source of data to understand complex cellular mechanisms and establish a molecular diagnosis of several diseases [5, 6].

In this sense, considering the miRNAs proprieties and their role in the post-transcriptional regulation of genic expression, along the recent years we observed a successive accumulation of new evidence from differential expression of miRNAs in physiological and pathological conditions—including in infectious diseases and during the cancer development [7,8,9,10,11,12,13,14].

Classically, miRNAs can modulate the genic expression acting directly by intracellular mechanisms or after their release into microvesicles, allowing the modulation of gene expression between different tissues [15,16,17]. Both intra- and extracellular miRNAs can be detected on tissue samples and biological fluids (as serum, plasma, urine, saliva, sweat, and tears), but currently, this methodology is poorly explored in personalized medicine as diagnosis strategy or therapeutic tool [18,19,20]. Thereby, this review explores the role of miRNAs on the maintenance of tissue homeostasis, during cancer development, the major strategies adopted to detect and quantify these molecules, and their potential application as biomarkers for early cancer detection using a tissue or minimally invasive samples. Taken together, these findings may contribute to the development of new diagnostic tools for the quantification of miRNAs using clinical samples and allowing the application of personalized medicine strategies.

The current paper summarizes the latest findings related to the application of miRNAs as biomarkers for cancer detection, notably breast, prostate, and cervical cancers. These cancers, despite their high incidence worldwide, resulting in millions of new diagnoses and deaths every year worldwide [21, 22], present only few studies summarizing the recent findings in this area. Besides, we take an overview of current strategies used to quantify these molecules in tissue samples and liquid biopsies and point out the major challenges to applying these strategies as a screening method for early cancer detection.

The biological basis of miRNAs and their use as biomarkers of cancer development

Role of miRNAs during tissue homeostasis, extracellular signaling and their implication on the development of cancer

During physiological conditions, miRNAs play a key role in the control of tissue homeostasis and cell signaling, acting as a post-transcriptional mechanism of gene expression. The coordinate function of these molecules associated with other mechanisms avoid the development of aberrant cellular proliferation, regulates the cellular differentiation and allows the fine regulation of mRNAs in response to endocrine hormones and other stimuli (e.g., cytokines, chemokines, infectious or stress conditions) detected in the cellular microenvironment [

Fig. 3
figure 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

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Taken together, these advances may represent a new era in cancer diagnosis procedures. As observed in several industry segments, the revolution 4.0 in health practices and devices can subvert the rationale of investments (from hospitalization to primary care assistance), contributing to early diagnosis and optimizing the resources available [95, 169, 170].