The Study On Function And Mechanism Of MiR-423 In The Cell Proliferation And Cell Cycle Of Liver Cancer

MicroRNAs (miRNAs) are 21-25 nucleotides, small non-coding RNA molecules expressed in a variety of eukaryotes, which are highly conserved across mammals, worms and flies. MiRNAs regulate gene expression at the post-transcriptional level through degradation or translational repression of their target messenger RNAs(mRNAs). Recent findings suggested that miRNAs play crucial roles in cell proliferation, cell death, metabolism and development. Increasing evidences indicate that the aberrantly expressed miRNAs may be involoved in human cancer, and may be useful for diagnosis and therapy of cancer. In addition, many miRNAs were localized to the chromosome firagile sites or related region in cancer, which are often involve in chromosome exchange, deletion, amplification or abnormal intergration. Chromosomal aberrations are often observed in liver cancer.In the former experiments of our laboratory, it was found that 129 miRNAs located in the chromosome firagile sites in liver cancer. Of these, we found that 22 miRNAs are often amplified or deleted in liver cancer. 17q11 is one of the chromosome firagile sites in liver cancer. Moreover, we identified that miR-423, located in 17q11, is high expressed in liver cancer.To study mechanism of miR-423 in liver cancer, we found miR-423 promoted cell growth and cell cycle transition at G₁/S, and further study found that it was induced by miR-423-3p, but not miR-423-5p.In addition,we have identified the miRNAs that modulate p21cip1/waf1 expression in the former experiments. miR-423-3p is one of the miRNAs. miR-423-3p exerts the function by directly targeting p21. Moreover , over-expression of miR-423 could induced resistance to 5-Fu in liver cancer cells . Our findings indicate aberrant expression of miR-423 is new mechanism of hepatocarcinogenesis and may allow us to develop new therapeutics against liver cancer.