MiR-1307 promotes ovarian cancer cell chemoresistance by targeting the ING5 expression

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.

The role of MicroRNA molecules and MicroRNA-regulating machinery in the pathogenesis and progression of epithelial ovarian cancer

“…AntagomiR MiR-1307 treatment of mice with xenograft tumors resulted in a decrease in tumor size and an even further decrease in tumor size with paclitaxel treatment (66). Treatment of xenograft mouse models with miR-192-DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) leads to inhibition of angiogenesis and tumor growth (67).…”

MicroRNAs in gynecological cancers: Small molecules with big implications

“…chemoresistance, is another characteristic of cancer cells responsible for making this disease particularly lethal. There are reports on a role of miRNAs in determining response to chemotherapies in GCs [240] (Table 4). Cisplatin and paclitaxel are two drugs that have been studied in detail in GCs, with regards to a role of miRNAs in determining sensitivity and/or acquisition of resistance.…”

Mir‐1307 regulates cisplatin resistance by targeting Mdm4 in breast cancer expressing wild type P53

“…Other research has reported that miR‐1307 could promote cell chemoresistance by targeting ING5 expression in ovarian cancer. Thus, miRNAs play an important role in drug resistance in cancer …”

“…Thus, miRNAs play an important role in drug resistance in cancer. 11 Whether miR-1307 is involved in drug resistance in breast cancer remains unclear. In this study, we investigate the roles of miRNAs in the development of drug resistance in human breast cancer cells.…”