Huaier Extract Inhibits Breast Cancer Progression Through a LncRNA-H19/MiR-675-5p Pathway.
BACKGROUND/AIMS
Increasing evidence indicates that Huaier extract has promising therapeutic effects against cancer. However, the mechanisms that underlie its anti-tumor effects remain unclear. In recent years, various studies have shown that long noncoding RNAs (lncRNAs) play a critical role in the regulation of cancer development and progression. Here, we explored the role of lncRNAs in Huaier-induced tumor suppression.


METHODS
Microarray profiling was performed to identify the candidate lncRNAs affected by Huaier extract. Quantitative realtime PCR (qPCR) was used to evaluate the transfection efficiency and the influence of Huaier extract on H19 expression. The effect of Huaier extract on the cell viability was examined by MTT. Moreover, the rates of apoptotic cells were detected using flow-cytometric analysis. Western blot analysis was applied to show the protein levels of CBL.


RESULTS
Microarray data derived from Huaier-treated breast cancer cells identified H19 as a potential target. Huaier extract reduced the expression of H19. The over-expression of H19 inhibited the cytotoxic effects of Huaier extract; in contrast, reduced H19 expression enhanced the function of Huaier extract. MiR-675-5p was identified as a mature product of H19. Moreover, Huaier extract reduced the miR-675-5p expression. Upregulating miR-675-5p reversed the inhibitory effects of Huaier extract, whereas downregulating miR-675-5p sensitized breast cancer cells to the effect of Huaier extract. In addition, Huaier extract increased the expression of CBL protein, a direct target of miR-675-5p.


CONCLUSION
Collectively, the data demonstrate that Huaier extract reduces viability and induces apoptosis in breast cancer cells via H19-miR-675-5p-CBL axis regulation.
['Wang|Jijun|J|', 'Wang|Xiaolong|X|', 'Chen|Tong|T|', 'Jiang|Liyu|L|', 'Yang|Qifeng|Q|']
D000070416:Antagomirs D017209:Apoptosis D001943:Breast Neoplasms D045744:Cell Line, Tumor D049109:Cell Proliferation D045424:Complex Mixtures D018450:Disease Progression D005260:Female D006801:Humans D061986:MCF-7 Cells D008516:Medicine, Chinese Traditional D035683:MicroRNAs D050721:Proto-Oncogene Proteins c-cbl D034622:RNA Interference D062085:RNA, Long Noncoding D034741:RNA, Small Interfering D015398:Signal Transduction D055454:Trametes
Huaier Breast cancer MiR-675-5p H19 CBL