MiRNA-29: A microRNA Family with Tumor-Suppressing and Immune-Modulating Properties

Abstract

MicroRNAs (miRNAs) are ubiquitously expressed small, non-coding RNAs that negatively regulate gene expression at a post-transcriptional level. So far, over 1000 miRNAs have been identified in human cells and their diverse functions in normal cell homeostasis and many different diseases have been thoroughly investigated during the past decade. MiR-29, one of the most interesting miRNA families in humans to date, consists of three mature members miR-29a, miR-29b and miR-29c, which are encoded in two genetic clusters. Members of this family have been shown to be silenced or down-regulated in many different types of cancer and have subsequently been attributed predominantly tumor-suppressing properties, albeit exceptions have been described where miR-29s have tumor-promoting functions. MiR-29 targets expression of diverse proteins like collagens, transcription factors, methyltransferases and others, which may partake in abnormal migration, invasion or proliferation of cells and may favor development of cancer. Furthermore, members of the miR-29 family can be activated by interferon signaling, which suggests a role in the immune system and in host pathogen interactions, especially in response to viral infections. In this review, we summarize current knowledge on the genomic organization and regulation of the miR-29 family and we provide an overview of its implication in cancer suppression and promotion as well as in host immune responses. The numerous remarkable properties of these miRNAs and their often altered expression patterns might make the miR-29 family promising biomarkers and therapeutic targets for various diseases in future.

Loss of miR-29b following Acute Ischemic Stroke Contributes to Neural Cell Death and Infarct Size

“…3 Silencing of members of the miR-29 family have been directly implicated in several types of cancer indicating their tumor-suppressive properties. 35 Lowering of miR-29b in myoblasts causes muscular dystrophy, which can be rescued by miR-29b delivery. In this scenario, miR-29 is under negative regulation by transforming growth factor-b signaling.…”

Aptamer-hybrid nanoparticle bioconjugate efficiently delivers miRNA-29b to non-small-cell lung cancer cells and inhibits growth by downregulating essential oncoproteins

“…Members of miRNA-29 family have been known to play an important role in cancer by regulating cell differentiation, proliferation, apoptosis, invasion, and migration. 4,5 However, clinical application of this relatively novel therapeutic faces many challenges, including degradation in serum, rapid blood clearance, stimulation of immune response, off-target effects, and poor cellular uptake. 6 Recently, our group developed a novel targeted hybrid nanoparticle delivery system.…”

“…12 Previous studies have demonstrated that miRNA-29b plays an important role in cancer by regulating cell proliferation, differentiation, and apoptosis. 5,6,13,14 It is usually silenced or downregulated in lung cancer and other types of cancer. 6,15 In contrast, forced expression in acute myeloid leukemia and lung cancer resulted in significant reduction of DNMT3B at both protein and mRNA levels by direct interaction.…”

“…miRNA-29b was selected as a model miRNA since it has been previously reported that miRNA-29b, a tumor suppressor miRNA, is aberrantly expressed in NSCLC and its perturbation is related to tumor development and progression. [4][5][6]19 Hence, miRNA-29b has been identified as an attractive candidate for miRNA-based therapeutics in NSCLC.…”

“…29 miRNA-29b has been reported to exert its tumor-suppressive role by directly targeting DNMT3b in cancer cells. 5,6,29 Furthermore, miRNA-29b has been reported to be downregulated in malignant cells, whereas MCL1 was upregulated. 5,6,30 MCL1 is a potent antiapoptic protein of the BCL-2 family.…”