Epigenetically regulated microRNAs and their prospect in cancer diagnosis

Abstract

Epigenetic alterations have been reported to deregulate the expression of many transcripts, including noncoding RNAs that have no apparent protein-coding capacity. Recently, as the result of numerous studies focused on miRNAs, novel sequencing technologies have made available the transcription profile of the entire human genome. miRNAs as drivers of tumor-suppressive and oncogenic functions have been found to be dysregulated in numerous cancer types. However, the functions of epigenetically regulated genetic elements other than protein-coding genes are still a matter of debate. In this review, the authors focus mainly on describing the epigenetic regulation of miRNAs in cancer. They also discuss the role of miRNAs as potential diagnostic and/or prognostic biomarkers.

Keywords::

• biomarker
• cancer
• epigenetics
• miRNA
• noncoding RNA
• prognosis

Acknowledgements

The authors thank Michael Worley and the Department of Scientific Publications at The University of Texas MD Anderson Cancer Center for expert editorial assistance.

Financial & competing interests disclosure

GA Calin is The Alan M. Gewirtz Leukemia & Lymphoma Society Scholar. He was also supported as a Fellow at The University of Texas MD Anderson Research Trust and as a University of Texas System Regents Research Scholar. Work in Calin’s laboratory is supported in part by the NIH/NCI (CA135444), a Department of Defense Breast Cancer Idea Award, Developmental Research Awards in Breast Cancer, Ovarian Cancer, Brain Cancer, Prostate Cancer, Multiple Myeloma, Leukemia (P50 CA100632) and Head and Neck (P50 CA097007) SPOREs, a SINF MDACC_DKFZ grant in CLL, a SINF grant in colon cancer, by the CLL Global Research Foundation, the Laura and John Arnold Foundation, the RGK Foundation, and the Estate of C. G. Johnson, Jr. The activity of I Berindan-Neagoe was partially financed by a POSCCE grant (709/2010) titled Clinical and Economical Impact of Proteome and 67e66ytTranscriptome Molecular Profiling in Neoadjuvant Therapy of Triple Negative Breast Cancer (BREASTIMPACT). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• miRNAs are classified as a class of noncoding RNA transcribed from non-protein-coding regions of the genome.

• miRNAs function throughout post-transcriptional gene silencing in general.

• Some key miRNAs regulate the expression levels of hundreds of genes simultaneously.

• Multiple miRNAs regulate their targets cooperatively.

• miRNAs function as oncogenes or tumor-suppressor genes.

• miRNAs are subject to the epigenetic regulatory mechanisms, the same as conventional protein-coding genes.

• Some miRNAs can target epigenetic factors in cancer.

• Epigenetically regulated miRNAs have been implicated as diagnostic and/or prognostic markers for cancer patients.

• miRNA-expression profiling with respect to epigenetics is likely to lead to new cancer diagnostic and treatment applications.