MiR-223 modulates hepatocellular carcinoma cell proliferation through promoting apoptosis via the Rab1-mediated mTOR activation
- Comprehensive Liver Cancer Center, The 302 Hospital, Beijing (China)
- Department of General Surgery, The 302 Hospital, Beijing (China)
- Department of Pathology, The 302 Hospital, Beijing (China)
- Department of Nursing, The 302 Hospital, Beijing (China)
Hepatocellular carcinoma (HCC) is a common digestive malignancy. MiR-223, a well-identified miRNA, exhibits diverse properties in different cancers. In this study, we demonstrated that miR-223 could suppress cell growth and promote apoptosis in HepG2 and Bel-7402 HCC cell lines. We screened and identified a novel miR-223 target, Ras-related protein Rab-1(Rab1). Upregulation of miR-223 would specifically and markedly down-regulate Rab1 expression. In addition, miR-223-overexpressing subclones showed significant cell growth inhibition by increasing cell apoptosis in HepG2 and Bel-7402 cells. To identify the mechanisms, we firstly investigated the mTOR pathway and found that pmTOR, p70S6K and Bcl-2 were dramatically down-regulated after miR-223 transfection, while no changes in the level of Bax was visualized. Furthermore, our data showed that the anti-tumor effects arising from miR-223 transfection in HCC cells may be due to the deactivation of mTOR pathway caused by the suppression of Rab1 expression when miR-223 is overexpressed. In summary, our results indicate that miR-223 functions as a tumor suppressor and plays a critical role in inhibiting the tumorigenesis and promoting the apoptosis of HCC through the mTOR signaling pathway in vitro. By targeting Rab1, miR-223 efficiently mediates the mTOR pathway. Given these, miR-223 may be a potential therapeutic target for treating HCC. - Highlights: • miR-223 is downregulated in hepatocellular carcinomas. • Rab1 is a novel downstream target of miR-223. • miR-223 suppressed cell growth and enhanced apoptosis in HepG2 and Bel-7402 cells. • miR-223 modulated mTOR signaling pathway by targeting Rab1.
- OSTI ID:
- 22696842
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 483, Issue 1; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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