Salivary MicroRNAs (miRNAs) Expression and its Implications as Biomarkers in Oral Cancer

Abstract

Oral cancer is a major public health concern in Asian countries, with India alone contributing 34% of the global incidence. Oral squamous cell carcinoma (SCC) is the most common. Carcinogenesis is a complex process in the development and progression of cancer. Delay in oral cancer diagnosis remains one of the major causes of high morbidity and mortality. Non-invasive methods such as liquid biopsy are being explored as biomarkers in the body fluid of individuals affected by oral cancer. Small non-coding RNAs called microRNAs (miRNAs) regulate gene expression, which plays an important role in the pathogenesis of cancer. This short communication further enlightens the knowledge of miRNA and its implications for oral cancer.

BACKGROUND

MicroRNAs (miRNAs) are small, evolutionary conserved, typically around 20–22 nucleotides long non-coding RNA, and are abundantly present in all human cells. miRNA dysregulation has an important role in the molecular pathogenesis of cancer in humans. Squamous cell carcinoma (SCC) is the most common type of oral cancer, accounting for most oral malignancies. Dysregulated miRNAs are present in various body fluids like plasma, serum, saliva, or urine and thus help in non-invasive diagnosis and prognosis of cancer.[¹²]

MicroRNAs present in saliva can be used for mass screening individuals with suspicious premalignant lesions.[³]

They provide molecular support for the individualized treatment of cancer patients. Therefore, finding abnormally expressed salivary miRNAs in OSCC and analyzing their correlation with the prognosis of OSCC contribute to improving the clinical outcomes of the patients.[⁴]

BIOGENESIS AND FUNCTION

The biogenesis of miRNA is classified into two pathways [Figure 1].

Figure 1: Biogenesis of miRNA (Adapted from Dai and Zhou, Bioinformatics 2010 Iss. 2.pg. 29-39)

1. Canonical
2. Non-canonical pathway

The canonical pathway is the dominant pathway by which miRNAs are produced. In this pathway, biogenesis occurs in the cytoplasm where pri-miRNA cleaves and produces pre-miRNA with the help of Drosha and DiGeorge Syndrome Critical Region 8 (DGCR8).[⁵] The non-canonical pathway usually uses combinations of proteins such as Drosha, Dicer, Exportin, and AGO2.

SALIVARY MIRNA AS A BIOMARKER IN ORAL CANCER

Saliva is a complex biological fluid secreted by salivary glands. It has a lubricating and antibacterial action. Saliva is a potential tool for the surveillance of general health and disease and oral cancer screening.[⁶]

To get a reproducible and reliable value, the technique must be standardized. The drawback of miR analysis is mainly due to expensive detection and analysis (e.g., RT-qPCR) technologies and the absence of valid endogenous RT-qPCR control. The lack of suitable endogenous control and matched clinical groups are challenges in miRNA research.

MICRORNAS AS PROGNOSTIC BIOMARKERS AND THERAPEUTIC ROLE IN ORAL CANCER

miRNAs play an important role in gene regulation, mRNA stability, translation, and transcription. They facilitate tumor progression and pathogenesis. Various cancer-specific miRNA is entrapped in the exosomes. miR-21 is a common microRNA that invariably increases in all cancers. Studies must be conducted in a large population of different ethnic origins to obtain complex miRNA dysregulation.

miRNA-based cancer therapeutics is an upcoming area presenting a promising research arena in the last few years to provide tumor-specific miRNA delivery. For therapeutic purposes, miRNAs are carried by a vehicle mainly with the help of nanoparticles. Further, the use of the different types of nanoparticles is under research, and important concern is to decrease toxicity and cellular accumulation. Various clinical trials related to miRNAs are underway, and there is still a long way to go. One needs to address the side effect and prognosis of the current therapeutic options.

CONCLUSION

Saliva diagnostics or liquid biopsy is a novel method used in diagnosis and prognosis, which is likely to offer a valid alternative shortly to arrive at clinical decisions and help predict post-treatment outcomes. Understanding the steps, methodologies, reporting, and evaluation protocols will help researchers to reduce bias in biomarker research. The research should focus on distinguishing biomarkers for cancer detection and therapeutics, reducing patient morbidity and mortality.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.