Abstract
The revelation that microRNAs (miRNAs) exist within the human genome uncovered an underappreciated mechanism of gene expression. For cells to regulate expression of their genes, miRNA molecules and argonaute proteins bind to mRNAs and interfere with efficient translation of the RNA transcript. Although miRNAs have important roles in normal tissues, miRNAs may adopt aberrant functions in malignant cells depending on their classification as either a tumor suppressor or oncogenic miRNA. Within this review, the current status of miRNA regulation is described in the context of signaling through the lysophosphatidic acid receptors, including the lysophosphatidic acid-producing enzyme, autotaxin. Thus far, research has revealed miRNAs that increase in response to lysophosphatidic acid stimulation, such as miR-21, miR-30c-2-3p, and miR-122. Other miRNAs inhibit the translation of lysophosphatidic acid receptors, such as miR-15b, miR-23a, and miR200c, or proteins that are downstream of lysophosphatidic acid signaling, such as miR-146 and miR-21. With thousands of miRNAs still uncharacterized, it is anticipated that the complex regulation of lysophosphatidic acid signaling by miRNAs will continue to be elucidated. RNA-based therapeutics have entered the clinic with enormous potential in precision medicine. This exciting field is rapidly emerging and it will be fascinating to witness its expansion in scope.
Highlights
Introduction to MiRNAsMicroRNAs are endogenous, non-translated RNAs comprised of ~22 nucleotides that regulate gene expression [1,2]
The first published report between lysophosphatidic acid and miRNA described the role of miR-30c-2*, which is denoted miR-30c-2-3p, and its actions as part of a feedback loop regulating signaling
Lysophosphatidic acid stimulation of ovarian cancer cells produces the transcription of numerous miRNAs, a significant abundance of miR-30c-2-3p, which functionally reduces cell viability and proliferation and facilitates cell death [52]
Summary
MicroRNAs (miRNAs) are endogenous, non-translated RNAs comprised of ~22 nucleotides that regulate gene expression [1,2]. MiRNAs bind to the 30 -untranslated region of many mRNAs and thereby silence gene expression by interfering with translation [3]. The binding fundamental binding interaction regulates interference the transcriptional dependent upon the base pairingupon between the seed region of the miRNA with the. 3 -untranslated interference is largely dependent the base pairing between the seed region of the miRNA with region of the mRNA These interactions destabilize pairing is likely among bases 13–16, as depicted in the schematic These interactions destabilize the mRNA and inhibit transcript processing. Note that imperfect base pairing is expected among the the mRNA and inhibit transcript processing. Note that imperfect base pairing is expected among the other sequences in the miRNA strand and does not detract from its function. Caenorhabditis elegans (C. elegans), prior to the establishment of conventional nomenclature [8,9]
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