Abstract
MicroRNA-124 (miR-124) is strongly expressed in neurons, and its expression increases as neurons mature. Through DNA methylation in the miR-124 promoter region and adsorption of miR-124 by non-coding RNAs, miR-124 expression is known to be reduced in many cancer cells, especially with high malignancy. Recently, numerous studies have focused on miR-124 due to its promising tumor-suppressive effects; however, the overview of their results is unclear. We surveyed the tumor-suppressive effect of miR-124 in glial cell lineage cancers, which are the most frequently reported cancer types involving miR-124, and in lung, colon, liver, stomach, and breast cancers, which are the top five causes of cancer death. Reportedly, miR-124 not only inhibits proliferation and accelerates apoptosis, but also comprehensively suppresses tumor malignant transformation. Moreover, we found that miR-124 exerts its anti-tumor effects by regulating a wide range of target genes, most notably STAT3 and EZH2. In addition, when compared to the original role of miR-124 in neuronal development, we found that the miR-124 target genes that contribute to neuronal maturation share similarities with genes that cause cancer cell metastasis and epithelial-mesenchymal transition. We believe that the two apparently unrelated fields, cancer and neuronal development, can bring new discoveries to each other through the study of miR-124.
Highlights
MicroRNAs are short, single-stranded RNAs consisting of approximately20 nucleotides
Many miRNAs have been identified in many species. miRNAs play a role in regulating post-transcriptional gene expression by forming an RNA-inducible silencing complex, which binds complementarily to the 3 UTR of mRNAs and cleaves or represses translation of the mRNA
MiRNAs contribute to a wide range of processes, from morphogenesis to disease development, carcinogenesis, and its progression. miRNAs that promote cancer development are called oncomirs, while miRNAs that suppress cancer development are called tumor suppressive miRNAs
Summary
In 2007, the decreased expression of miR-124 was discovered to be caused by methylation of the CpG islands of the genomic region encoding miR-124 in colorectal cancer cells HCT-116 [12]. This finding led to the further discovery of the tumor-suppressive effect of miR-124. In addition to circRNAs, the long non-coding RNA, metastasis-associated lung adenocarcinoma transcript-1 (MALAT1), can adsorb miR-124 and promote non-small cell lung cancer [32,33], cervical cancer [34], and nasopharyngeal carcinoma [35], and is known to promote malignancy through increased expression of miR-124 target genes. A great variety of cancers create a more favorable environment for tumor growth either by suppressing miR-124 expression, by adsorbing miR-124, or in combination (Figure 1)
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