MicroRNAome genome: A treasure for cancer diagnosis and therapy

Abstract

The interplay between abnormalities in genes coding for proteins and microRNAs (miRNAs) has been among the most exiting yet unexpected discoveries in oncology over the last decade. The complexity of this network has redefined cancer research as these molecules produced from what was once considered “genomic trash”, have shown to be crucial for cancer initiation, progression, and dissemination. Naturally occurring miRNAs are very short transcripts that never produce a protein or amino acid chain, but act by regulating protein expression during cellular processes such as growth, development and differentiation at the transcriptional, post-transcriptional and/or translational level. In this review article we present miRNAs as ubiquitous players involved in all cancer hallmarks. We also describe the most used methods to detect their expression, which have revealed through gene expression studies the identity of hundreds of miRNAs dysregulated in cancer cells or tumor microenvironment cells. Furthermore, we discuss the role of miRNAs as hormones and as reliable cancer biomarkers and predictors of treatment-response. Along with this, we explore current strategies in designing miRNA-targeting therapeutics, as well as the associated challenges that research envisions to overcome. Finally, we introduce a new wave in molecular oncology translational research, the study of long non-coding RNAs.

A miRNAs panel promotes the proliferation and invasion of colorectal cancer cells by targeting GABBR1

“…Many miRNAs are involved in the regulation of cell proliferation in many kinds of physiological processes 25, 26, 27, 28.In colorectal cancer, miRNAs have been the potential biomarkers of colorectal cancer 29, 30.miR‐106a/b, miR‐20a/b, miR‐17 are the members of miR‐17‐92 cluster and have been demonstrated to participate into the signaling pathways to regulate the initiation and development of cancers 31. miR‐106b promoted colorectal cancer cell migration and invasion by directly targeting DLC1 20.miR‐106a also has been reported to play an oncogenic role in pancreatic cancer 32.…”

Cell‐to‐cell communication: microRNAs as hormones

“…Abnormal expression of specific miRNAs was observed during the progression of several types of cancer (Fabbri et al ., 2008). Accumulating evidence demonstrates that specific miRNAs hold great promise as novel biomarkers for clinical diagnosis of many types of diseases, including cancer (Berindan‐Neagoe et al ., 2014). Especially, circulating miRNAs are remarkably stable in the blood.…”

Epigenetic regulation by DNA methylation and miRNA molecules in cancer

“…Aberrant expression profiles of miRNAs have been found directly associated with human diseases, such as autoimmune and cardiac disorders, and schizophrenia, and are highly dysregulated in cancer. A different miRNA expression has been found between normal and benign or malignant tissue including leukemias, lymphomas; lung, breast, colorectal cancers (CRCs), papillary thyroid carcinomas, glioblastomas and other brain tumors, hepatocellular carcinomas, pancreatic tumors, cervical cancers, prostate cancers, kidney and bladder cancers or pituitary adenomas [11].…”

“…PrimiRNAs are processed into stem-loop precursors of approximately 70 nt miRNAs (pre-miRNAs) by the microprocessor complex consisting of RNase III enzyme -DROSHA. Pre-miRNAs are then exported to the cytoplasm where the RNAse III endonuclease -Dicer -cleaves the pre-miRNAs to produce two mature miRNAs, of which one is usually degraded [11]. Mature miRNAs are thought to be extremely stable molecules with little evidence for active degradation.…”