Abstract
BackgroundWe aimed to investigate the function of miR-1307 in chemoresistance and to explore its chemoresistance mechanism in ovarian cancer.MethodsIC50 determination was used to test the chemoresistance profling in ovarian cancer cells. QRT-PCR or western blot was used to validate the expression level of miR-1307 and candidate gene or protein. Colony formation assay and FITC-labeled enhanced Annexin V immunofluorescence were used to compare cell proliferation and apoptosis ability, respectively. The potential target gene and its biological function of miRNA-1307 were also analyzed. Bioinformatics and Luciferase Reporter Gene Assay were conducted to validate the regulation of miRNA-1307 on the ING5 expression. Xenografts assay was used to demonstrate the inhibiting effect of miR-1307 ASO and Taxol therapy against ovarian cancer in vivo.ResultsMiR-1307 was over-expressed in chemoresistant ovarian cancer cell line A2780/Taxol, and over-expression or loss of miR-1307 promoted or inhabited chemoresistance. And we also found that the over-expression of miR-1307 promoted proliferation and inhibited apoptosis in ovarian cancer cells. Besides, we demonstrated that ING5 was a direct target of miR-1307 and miR-1307 down-regulated the ING5 expression in ovarian cancer cells. Additionally, we showed that ING5 inhibited cell proliferation, promoted cell apoptosis and inhabited chemoresistance reversely. Furthermore, the up-regulated ability of cell apoptosis and down-regulated ability of chemoresistance following the loss of miR-1307 was reversed by adding ING5 siRNA in vitro. Finally, we proved the inhibiting effect of miR-1307 ASO and Taxol therapy by increasing the ING5 expression against ovarian cancer through xenografts assay in vivo.ConclusionOur results suggested that miR-1307 could promote ovarian cancer chemoresistance by targeting the ING5 expression and miR-1307 might serve as a therapeutic target for ovarian cancer.
Highlights
We aimed to investigate the function of miR-1307 in chemoresistance and to explore its chemoresistance mechanism in ovarian cancer
MiR-1307 was over-expressed in chemoresistant ovarian cancer cell line A2780/taxol, and over-expression or loss of miR-1307 promoted or inhabited chemoresistance To prove the characteristics of chemoresistant ovarian cancer cells, we showed the Half maximal inhibitory concentration (IC50) difference between the A2780 and A2780/Taxol cells: IC50 in the chemoresistant A2780/Taxol cells was much bigger than that in the A2780 cells (P < 0.01, Fig. 1a)
Our results indicated that miR-1307 was over-expressed in chemoresistant ovarian cancer cell A2780/Taxol, and perhaps miR-1307 promoted cell chemoresistance in cell A2780/Taxol compared to cell A2780 (P < 0.01, Fig. 1a)
Summary
We aimed to investigate the function of miR-1307 in chemoresistance and to explore its chemoresistance mechanism in ovarian cancer. MiRNAs have been reported to either promote carcinogenesis by inhibiting tumor suppressors or suppress tumor development by acting as down-regulate oncogenes in ovarian cancer: downregulated miRNAs (including let-7a/b/d/f, miR-31, 34abc, 92a, 99b, 125b, 127, 152, 155 and 199a), and over-expressed oncogenic miRNAs (such as miR18a, 20a, 21, 23a/b, 29a, 92, 93, 126, 141, 199a-3p, 200b/c and 429) [2, 8,9,10,11,12]. Two studies have reported that miRNA is involved in the development of chemoresistance in ovarian cancer by inhibiting proapoptotic signal pathway [4, 8]. It has been reported that miRNA-1307 is over-expressed in chemoresistant ovarian cancer tissues compared to the chemosensitive counterparts, indicating that miR-1307 is associated with the chemoresistance in ovarian cancer [7]. Up to now, the functional study of miR-1307 has been limited, and the chemoresistance mechanism of miR-1307 in ovarian cancer is still unclear
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