MiR1425p promotes hepatocellular carcinoma cell apoptosis induced by dexorubicin with targetting
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Abstract:
Objective:To investigate the function and molecular mechanisms of micro RNA1425p ( miR1425p) on the doxorubicin induced apoptosis of primary hepatocellular carcinoma (HCC).Methods: Paired HCC tissues and adjacent noncancerous tissue specimens (25cm away from the lesion) were surgically collected from 88 patients who were diagnosed with primary HCC in Tumor Hospital Affiliated to Guangxi Medical University between October 2001 and July 2005. qRTPCR was used to detect the miR1425p expressions in those HCC tissues, adjacent noncancerous tissues, normal hepatocellular cell line and HCC cell lines. HCC SMMC7721 cells were transfected with miR1425p mimics, and flow cytometry was used to determine the changes in doxorubicin (1 μg/ml) induced apoptosis of SMMC7721 cells. Bioinformatics predicted that miR1425p could bind with insulinlike growth factor 2 Mrnabinding protein 3 (IGF2BP3), which was then validated by luciferase reporter gene assay. qRTPCR and Western blotting were separately used to detect the mRNA and protein expressions of IGF2BP3 in SMMC7721 cells that overexpress miR1425p. Results: Compared with the adjacent nontumor tissues, miR1425p was significantly lower in HCC tissues (-6.91±261 vs -11.59±259, P<0.01) and this decrease was also found in HCC cell line compared with normal human liver cells (P<0.01); overexpression of miR1425p significantly promoted the doxorubicin induced apoptosis of HCC SMMC7721 cells (\[49.4±3.47\]% vs \[19.50±1.74\]%, P<0.01). miR1425p overexpression could obviously inhibit the mRNA and protein expressions of IGF2BP3 in SMMC7721 cells. Luciferase reporter gene assay also showed that miR1425p overexpression could inhibit the luciferase activity of 3′UTR of IGF2BP3. Conclusion: miR1425p expression significantly decreased in both HCC tissues and HCC cell lines. miR1425p mimics transfection promoted doxorubicin induced apoptosis of HCC cells, and the mechanism probably related with miR1425p targetting IGF2BP3 and further promote the apoptosis of HCC cells.
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Project supported by the National Natural Science Foundation of China (No.31390431), and the National Key Basic Research and devepment Program (973) of China (No.2013CB530503)