Abstract
Renal cell carcinoma (RCC) is one of the most common renal malignancies in the urinary system. Numerous studies have demonstrated that miRNAs can regulate tumorigenesis and progression. This study aims to investigate the role and regulatory mechanism of miR-6838-5p in RCC. Our study confirmed that miR-6838-5p was upregulated in human RCC tissues (30/42, 77.43%, P < 0.01) and RCC cell lines (P < 0.05) compared to adjacent non-neoplastic tissues and normal renal epithelial cells. In vitro, overexpression of miR-6838-5p enhanced cell proliferation and invasion in human RCC cell lines (ACHN and 786-O), which were detected by CCK-8, Transwell and Colony formation assays (P < 0.05), and knockdown of miR-6838-5p suppressed cell proliferation and invasion (P < 0.05). Results of Bioinformatics analysis combined with Dual-luciferase reporter gene assay demonstrated that miR-6838-5p could bind to Cyclin D binding myb-like transcription factor 1 (DMTF1). In addition, RT-qPCR and Western blotting confirmed that DMTF1 was downregulated in RCC tissues and cell lines. Meanwhile, it was demonstrated that overexpression of miR-6838-5p inhibited DMTF1 level in ACHN cells. Next, we confirmed that DMTF1 overexpression reversed the inhibitory effects of overexpression of miR-6838-5p on phosphatase and tensin homolog (PTEN), tumor protein 53(p53), murine double minute 2 (MDM2) and alternative reading frame (ARF) protein levels in the ARF-p53 signaling pathway. In conclusion, our research showed that miR-6838-5p enhanced the proliferation and invasion of RCC cells by inhibiting the DMTF1/ARF-p53 axis.
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Data availability
The datasets used during the present study are available from the corresponding author upon reasonable request.
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JZ designed the study. XQZ and YW drafted and wrote the manuscript. DZ and HCL collected and analyzed the data. TC and JZ contributed samples collection and intellectual input. JZ revised the manuscript critically for intellectual content. All authors gave intellectual input to the study and approved the final version of the manuscript.
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Zhai, X., Wu, Y., Zhang, D. et al. MiR-6838-5p facilitates the proliferation and invasion of renal cell carcinoma cells through inhibiting the DMTF1/ARF-p53 axis. J Bioenerg Biomembr 53, 191–202 (2021). https://doi.org/10.1007/s10863-021-09888-2
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DOI: https://doi.org/10.1007/s10863-021-09888-2