Journal
ASIAN PACIFIC JOURNAL OF CANCER PREVENTION
Volume 15, Issue 23, Pages 10439-10444Publisher
ASIAN PACIFIC ORGANIZATION CANCER PREVENTION
DOI: 10.7314/APJCP.2014.15.23.10439
Keywords
Hepatocellular carcinoma cell lines; miR-340; Nrf2; cisplatin; chemoresistance
Categories
Funding
- National Basic Research Program of China (973 Program) [2012CB720605]
- Zhejiang Provincial Natural Science Foundation of China [LQ13H160021, LY12H20001]
- Wenzhou Municipal Science and Technology Bureau [Y20120125]
Ask authors/readers for more resources
Many chemotherapeutic agents have been successfully used to treat hepatocellular carcinoma (HCC); however, the development of chemoresistance in liver cancer cells usually results in a relapse and worsening of prognosis. It has been demonstrated that DNA methylation and histone modification play crucial roles in chemotherapy resistance. Currently, extensive research has shown that there is another potential mechanism of gene expression control, which is mediated through the function of short noncoding RNAs, especially for microRNAs (miRNAs), but little is known about their roles in cancer cell drug resistance. In present study, by taking advantage of miRNA effects on the resistance of human hepatocellular carcinoma cells line to cisplatin, it has been demonstrated that miR-340 were significantly downregulated whereas Nrf2 was upregulated in HepG2/ CDDP (cisplatin) cells, compared with parental HepG2 cells. Bioinformatics analysis and luciferase assays of Nrf2-3'-untranslated region-based reporter constructor indicated that Nrf2 was the direct target gene of miR340, miR-340 mimics suppressing Nrf2-dependent antioxidant pathway and enhancing the sensitivity of HepG2/ CDDP cells to cisplatin. Interestingly, transfection with miR-340 mimics combined with miR-340 inhibitors reactivated the Nrf2 related pathway and restored the resistance of HepG2/CDDP cells to CDDP. Collectively, the results first suggested that lower expression of miR-340 is involved in the development of CDDP resistance in hepatocellular carcinoma cell line, at least partly due to regulating Nrf2-dependent antioxidant pathway.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available