ALKBH5 inhibited autophagy of epithelial ovarian cancer through miR-7 and BCL-2.

BACKGROUND: ALKBH5 regulated the malignant behavior of breast cancer and glioblastoma. However, the expression and function of ALKBH5 in epithelial ovarian cancer have not yet been determined. In the present study, we investigated the expression and function of ALKBH5 in epithelial ovarian cancer with respect to its potential role in the tumorigenesis of the disease as well as an early diagnostic marker.

METHODS: Immunohistochemistry and western blot were used to detect protein expression. Gene silencing and over-expression experiment were used to study gene function. Cell proliferation assay and Matrigel invasion assays were used to detect cell proliferation and invasion, respectively. The nude mouse tumor formation experiment was used to evaluate the growth of cells in vivo.

RESULTS: The expression of ALKBH5 was found to be increased in epithelial ovarian cancer tissue as compared to the normal ovarian tissues. The silencing of ALKBH5 in SKOV3 cells enhanced the autophagy and inhibited the proliferation and invasion in vitro and in vivo, whereas the ectopic expression of ALKBH5 in A2780 cells exerted an opposite effect. Mechanical study revealed that ALKBH5 physically interacted with HuR. ALKBH5 activated EGFR-PIK3CA-AKT-mTOR signaling pathway. Also, ALKBH5 enhanced the stability of BCL-2 mRNA and promoted the interaction between Bcl-2 and Beclin1.

CONCLUSION: Overall, the present study identified ALKBH5 as a candidate oncogene in epithelial ovarian cancer and a potential target for ovarian cancer therapy.