Abstract
MicroRNAs (miRNAs) can be used to target a variety of human malignancies by targeting their oncogenes or tumor suppressor genes. Recent evidence has shown that miRNA-1208 (miR-1208) was rarely expressed in a variety of cancer cells, suggesting the possibility that miR-1208 functions as a tumor suppressor gene. Herein, ectopic expression of miR-1208 induced the accumulation of sub-G1 populations and the cleavage of procaspase-3 and PARP, which could be prevented by pre-treatment with the pan-caspase inhibitor, Z-VAD. In addition, miR-1208 increased the susceptibility to cisplatin and TRAIL in Caki-1 cells. Luciferase reporter assay results showed that miR-1208 negatively regulates TBC1 domain containing kinase (TBCK) expression by binding to the miR-1208 binding sites in the 3′-untranslated region of TBCK. In addition, miR-1208 specifically repressed TBCK expression at the transcriptional level. In contrast, inhibition of endogenous miR-1208 by anti-miRs resulted in an increase in TBCK expression. Downregulation of TBCK induced by TBCK-specific siRNAs increased susceptibility to cisplatin and TRAIL. These findings suggest that miR-1208 acts as a tumor suppressor and targets TBCK directly, thus possessing great potential for use in renal cancer therapy.
Highlights
MicroRNAs (MiRNAs), small molecules of single-stranded RNA with a length of 21–25 nucleotides, regulate gene expression and control many physiological processes such as development, proliferation, differentiation, and apoptosis [1,2]
Our study has demonstrated that miR-1208 induces apoptosis in Caki-1 cells by activating the caspase pathway
Transfection with miR-1208 was shown to enhance the sensitivity of Caki-1 cells to cisplatin and TNF-related apoptosis-inducing ligand (TRAIL)
Summary
MicroRNAs (MiRNAs), small molecules of single-stranded RNA with a length of 21–25 nucleotides, regulate gene expression and control many physiological processes such as development, proliferation, differentiation, and apoptosis [1,2]. A single miRNA can alter the expression of more than 100 different genes, controlling an entire cancer-specific signaling pathway [4]. Abnormalities in miRNA expression have been identified in all human tumors [5]. A better understanding of the molecular mechanisms involved in RCC tumorigenesis and the development of new therapeutic targets are urgently needed to improve RCC therapy. Combination therapy with miRNAs and anticancer agents can be effective for achieving a potent drug response when the miRNAs function as tumor suppressors by targeting several essential oncogenes [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
