microRNA cluster MC‐let‐7a‐1~let‐7d promotes autophagy and apoptosis of glioma cells by down‐regulating STAT3

Abstract

Background Accumulating evidence has highlighted the correlation between microRNAs (miRNAs) and the progression of glioma. However, the role of miR cluster MC‐let‐7a‐1 ~ let‐7d in glioma remains elusive. Thus, the current study aimed to investigate the effect of miR cluster MC‐let‐7a‐1 ~ let‐7d on glioma progression. Methods and Results Microarray data analysis provided data indicating the involvement of miR cluster MC‐let‐7a‐1 ~ let‐7d in glioma via STAT3. The expression of let‐7a‐1, let‐7d, let‐7f‐1, and miR cluster MC‐let‐7a‐1 ~ let‐7d was diminished in the glioma tissues and the cell lines. Additionally, our results revealed that STAT3 was a target gene of let‐7d, let‐7a‐1, and let‐7f‐1, which was further verified by the dual‐luciferase reporter gene assay. Moreover, STAT3 expression was negatively mediated by let‐7a‐1, let‐7d, and let‐7f‐1. Up‐regulated miR cluster MC‐let‐7a‐1 ~ let‐7d or silenced STAT3 suppressed cell proliferation but accelerated cell apoptosis and autophagy. Moreover, restrained tumor growth was identified in the nude mice treated with miR cluster MC‐let‐7a‐1 ~ let‐7d mimics or STAT3 siRNA. Conclusion Taken together, the miR cluster MC‐let‐7a‐1 ~ let‐7d promotes glioma cell autophagy and apoptosis by repressing STAT3. The current study highlights the potential of the miR cluster MC‐let‐7a‐1 ~ let‐7d as biomarkers and promising treatment strategies for glioma.

Upregulation of spinal ASIC1 by miR‐485 mediates enterodynia in adult offspring rats with prenatal maternal stress

“…Epigenetic factors such as DNA methylation, histone acetylation, and miRNAs are all reflections of changes in environmental stimuli 40,41 . MiRNA, a small RNA sequence, can play a major role in cell differentiation, biological development, and disease development by directly inhibiting target gene translation 42,43 . Recent years, there were literatures reported the roles of miRNAs in a variety of pregnancy‐related complications such as preeclampsia and FGR, indicating its importance in pregnancy 44,45 .…”

“…40,41 MiRNA, a small RNA sequence, can play a major role in cell differentiation, biological development, and disease development by directly inhibiting target gene translation. 42,43 Recent years, there were literatures reported the roles of miRNAs in a variety of pregnancy-related complications such as preeclampsia and FGR, indicating its importance in pregnancy. 44,45 In general, DNA methylation and histone acetylation are believed to regulate gene expression at mRNA levels while miRNAs are believed to regulate gene expression both at mRNA and protein levels.…”

Noncoding RNAs involved in the STAT3 pathway in glioma

“…A study confirmed that STAT3 was the direct target gene of these three let-7 miRNA dual luciferase reporters. Then, cell fluorescence staining and experiments in mouse models confirmed that miRNA clusters of let-7a-1 ~ let-7d acted as tumour suppressors in glioma [ 40 ]. In terms of migration and invasion, the growth and metastasis of GBM depend on the expression of matrix metalloproteinase 2 (MMP2).…”

Circulating RNAs as Potential Biomarkers in Amyotrophic Lateral Sclerosis

“…Let-7 family miRNAs are involved in multiple pathways contributing to cell survival and cell death and influence cancer risk and prognosis as well as neuroinflammation [153][154][155]. It was shown recently, that miR cluster MC-let-7a-1~let-7d promotes glioma cell autophagy and apoptosis by repressing signal transducer and activator of transcription 3 (STAT3) [156].…”