Abstract
MicroRNAs are small non-coding RNAs that regulate the expression of other genes in a post-transcriptional manner. MiR-34a can induce apoptosis, cell cycle arrest, and senescence. However, its role in tumor progress remains to be fully elucidated. In the present study, the role of miR-34a in lymphatic metastasis was investigated using mouse hepatocarcinoma cell lines Hca-F and Hepa1-6. MicroRNA profiling and Hairpin-RT-PCR analysis showed that the expression level of miR-34a was higher in Hepa1-6 cells (of no metastatic ability) than that in Hca-F cells (of high metastatic ability). Ectopic expression of miR-34a can inhibit cell growth and cell invasion in Hepa1-6 and Hca-F cells. Moreover, miR-34a triggers G1 arrest and down-regulates CyclinD1 and CDK6 in Hepa1-6 cells. Furthermore, we proved that miR-34a decreased adhesion of Hca-F cells to regional lymph node in vitro, reduced lymph nodes-metastasized burden, and inhibited tumor lymph node metastases in vivo. All these results suggest that miR-34a plays multiple tumor suppressive roles in murine hepatocarcinoma, not only inhibiting cell growth by cell cycle arrest, but also repressing metastasis, and may serve as a novel therapeutic target for hepatocarcinoma.
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