microRNA (miRNA) – Introduction

miRNA in situ hybridization for Cancer Precision Medicine: Role in pharmacogenomics, tumor grading and staging, differentiation, and cancers of unknown primary

Since their discovery, microRNAs (miRNAs) have emerged as crucial regulators of important cellular functions. The biogenesis of miRNA follows a complex path through a number of precursor forms resulting in mature, small, noncoding, single-stranded RNAs that are typically 20 to 40 nucleotides in length. Mature miRNA binds to a specific target sequence within a mRNA effecting post-translational regulation incellular processes such as development, differentiation, proliferation, metabolism, and apoptosis. Dysregulated cell signaling in many tumor types results in upregulation or downregulation of various miRNAs. These microRNAs function either as oncogenes or tumor suppressors. This dynamic role of miRNAs within various cell types gives them the potential to serve as promising biomarkers in diagnostic, prognostic and targeted therapy practices.

A major challenge in clinical diagnostics is to distinguish cancer types with poor differentiation. Poorly differentiated tumors exhibit very aggressive behavior and have poor prognosis. Thesetumors are difficult to diagnose at early stage due to late-onset symptoms, overlapping immunohistochemical profiles, and indistinguishable histological characteristics. Also, the uncertainties surrounding the diagnosis of cancers of unknown primary (CUPs) can lead to significant psychosocial distress for both the patient and family. CUPs are metastatic tumors for which no primary site has been identified, accounting for 3–5% of all diagnosed cancers. The inability to identify the tissue of origin in CUP patients creates diagnostic challenges because the primary site of cancer determines the treatment choices and overall prognosis. However, increasing understanding of molecular alterations underlying carcinogenesis has created opportunities for using miRNAs as diagnostic and prognostic indicators. In the era of precision medicine, it is essential to identify novel diagnostic biomarkers to improve the management of cancer treatment and increased patient care.

MicroRNAs are multifaceted and can be used as early-stage cancer detection markers, and for differentiation of malignant and benign tumors, identification of cancer of unknown primary (CUP), and differentiation of cancer subtypes. miRNA expression profiles can also be used for  grading, staging of cancer subtypes, and classifying undifferentiated and poorly differentiated tumors.