Levels of MicroRNA Heterogeneity in Cancer Biology

Abstract

MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression, involved in the silencing of messenger RNA (mRNA) translation. The importance of miRNA signatures in disease screening, prognosis, and progression of different tumor types and subtypes is increasing. miRNA expression levels change depending on numerous factors. In this review, we are describing the circumstances under which miRNA levels can change, these are named 'levels' of heterogeneity of miRNAs. miRNAs can have oncogenic, tumor suppressive, or both roles depending on tumor type and target mRNA whose translation they silence. The expression levels of a single miRNA may vary across different cancer types and subtypes, indicating that a miRNA signature may be tissue specific. miRNA levels of expression also vary during disease formation and propagation, indicating the presence of a time profile for their expression. The complexity of the miRNA-mRNA interference network mirrors different genetic and epigenetic changes that influence miRNA and mRNA availability to each other, and hence, their binding ability. The potential role of miRNAs as biomarkers is two-fold; first, for monitoring of the phases of cancer pathogenesis, and second, to characterize the particular type/subtype of cancer. It is important that a particular miRNA should be characterized by examining as many types and subtypes of cancers as are available, as well as being extracted from different types of samples, in order to obtain a complete picture of its behavior and importance in the disease pathology.

Dissimilar Appearances Are Deceptive–Common microRNAs and Therapeutic Strategies in Liver Cancer and Melanoma

“…Numerous studies have described so-called "miRNA signatures" associated with specific biological functions, including cancer development and progression [13,85,[98][99][100][110][111][112]. Since one miRNA can regulate up to hundreds of different target genes in a cell [69,113,114], the administration of single miRNAs as therapeutic targets raises the problem of a potentially widespread functional heterogeneity of one miRNA in different tumors types and potential adverse side effects to normal tissue [115,116]. Therefore, research addressing miRNAs as therapeutic targets should focus on miRNAs that majorly or desirably act solely as tumor-suppressors or oncogenes in one specific setting to avoid mutual neutralization effects.…”

Circulating cell‐free microRNAs in cutaneous melanoma staging and recurrence or survival prognosis

“…While approximately 300 miRNAs have demonstrated a role in carcinogenesis, more than 2000 miRNAs have been found differentially expressed in human cancers (Yang et al, 2017) and evidence that different types of cancer can be discriminated by miRNA profiling has been reported (Iorio & Croce, 2017;Petrovic, Ergün, & Isenovic, 2017). In cutaneous melanoma, there is increasing evidence for a significant role of specific miRNAs as oncogenes or tumour suppressor genes (Mione & Bosserhoff, 2015;Mirzaei et al, 2016;Varamo, Occelli, Vivenza, Merlano, & Lo Nigro, 2017) as well as their involvement in other aspects of melanoma biology (Leibowitz-Amit, Sidi, & Avni, 2012;Luo, Weber, Osen, Bosserhoff, & Eichmuller, 2014;Sun, Zhou, Majid, Kashani-Sabet, & Dar, 2014;Voller, Ott, & Bosserhoff, 2013).…”

Research progress on the relationship between zinc deficiency, related microRNAs, and esophageal carcinoma

“…Previous studies have shown that miRNA dysregulation is involved in the development of EC and that miRNAs act as both oncogenes and tumor suppressor genes. [16][17][18] He et al divided human EC cell lines KYSE170 and ECA109 into two groups: one cultured in RPMI 1640 medium containing 10% fetal bovine serum (FBS) and the other in RPMI 1640 medium containing 10% FBS plus 50 μM/L ZnSO 4 . The miRNA levels in the two cell lines were then measured to analyze the influence of the Zn level on the miRNAs.…”

“…Micro‐RNAs (miRNAs, miRs) are non‐coding RNAs approximately 18–22 nucleotides in length that post‐transcriptionally regulate gene expression by base‐pairing to partially complementary sequences in the 3′‐untranslated region (UTR) of their target messenger RNA (mRNA). Previous studies have shown that miRNA dysregulation is involved in the development of EC and that miRNAs act as both oncogenes and tumor suppressor genes …”