Abstract
Soon after microRNAs entered the stage as novel regulators of gene expression, they were found to regulate -and to be regulated by- the development, progression and aggressiveness of virtually all human types of cancer. Therefore, miRNAs in general harbor a huge potential as diagnostic and prognostic markers as well as potential therapeutic targets in cancer.The miR-17-92 cluster was found to be overexpressed in many human cancers and to promote unrestrained cell growth, and has therefore been termed onco-miR-1. In addition, its expression is often dysregulated in many other diseases. MiR-17-5p, its most prominent member, is an essential regulator of fundamental cellular processes like proliferation, autophagy and apoptosis, and its deficiency is neonatally lethal in the mouse. Many cancer types are associated with elevated miR-17-5p expression, and the degree of overexpression might correlate with cancer aggressiveness and responsiveness to chemotherapeutics – suggesting miR-17-5p to be an alarm signal. Liver, gastric or colorectal cancers are examples where miR-17-5p has been observed exclusively as an oncogene, while, in other cancer types, like breast, prostate and lung cancer, the role of miR-17-5p is not as clear-cut, and it might also act as tumor-suppressor.However, in all cancer types studied so far, miR-17-5p has been found at elevated levels in the circulation. In this review, we therefore recapitulate the current state of knowledge about miR-17-5p in the context of cancer, and suggest that elevated miR-17-5p levels in the plasma might be a sensitive and early alarm signal for cancer (‘alarmiR’), albeit not a specific alarm for a specific type of tumor.
Highlights
The role of miRNAs in human development, homeostasis and disease is well acknowledged
We thereby surprisingly found that it is elevated in the serum or plasma of a large variety of solid and hematologic tumor types, which prompts us to here postulate a function of circulating miR-17-5p as an alarm signal that is sensitive for tumors in general, albeit www.impactjournals.com/oncotarget not specific for a defined tumor type
In the context of biomarkers, miRNAs are considered as promising emerging biomarkers in cancer, especially when considering circulating miRNAs as minimally invasive analytes within liquid biopsies [16]
Summary
The role of miRNAs in human development, homeostasis and disease is well acknowledged. The E2F family of transcription factors like E2F1, E2F2 and E2F3 activates the genes that are involved in cell progression from G1 to S phase and are reported to be direct targets of miR-17-92 cluster.
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