Abstract
Emerging evidence has indicated that dysregulation of miR-362-3p is involved in the initiation and progression of several types of human cancers. However, the molecular mechanism of miR-362-3p in renal cell carcinoma (RCC) is still not completely clear. In this study, we found that miR-362-3p was frequently down-regulated in human RCC tissues. Overexpression of miR-362-3p in RCC cells significantly suppressed the proliferation, cell cycle and motility in vitro and in vivo via regulating AKT/FOXO3 signaling. We further confirmed that SP1 was a direct target of miR-362-3p. Knockdown of SP1 expression by a small interfering RNA (siRNA) phenocopied the effect of miR-362-3p overexpression in RCC cells. In conclusion, the current results provide evidence for the role of miR-362-3p in the pathogenesis of RCC and thus miR-362-3p may serve as an attractive candidate for RCC therapy.
Highlights
Renal cell carcinoma (RCC) is the sixth most common cancer in males and tenth in females worldwide (Siegel et al, 2018), with an estimated 338 thousand new cases and 144 thousand deaths annually (Ferlay et al, 2015)
Detection of miR-362-3p expression in renal cell carcinoma (RCC) tissue microarray (TMA) with Chromogenic in situ Hybridization (CISH) method demonstrated that miR-362-3p was significantly downregulated in RCC tissues than adjacent non-tumor tissues (Figures 1C,D)
AKT/FOXO3 Signaling Pathway Is Involved in miR-362-3p-Mediated Inhibition of Cell Proliferation and Motility
Summary
Renal cell carcinoma (RCC) is the sixth most common cancer in males and tenth in females worldwide (Siegel et al, 2018), with an estimated 338 thousand new cases and 144 thousand deaths annually (Ferlay et al, 2015). It is urgently warranted to identify novel molecular biomarkers to improve the clinical outcomes of RCC patients. MicroRNAs (miRNAs) are a conserved class of small non-coding RNAs (19–24 nucleotides) that regulate target gene expression by inducing mRNA degradation and/or suppressing mRNA translation (Bartel, 2004). Emerging evidence has demonstrated that miRNAs play a crucial role in tumorigenicity and progression in human cancers (Croce, 2009; Wang et al, 2018).
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