The addition of VEGF, IGF-1, and IL-8 weakened the inhibitory effect of DIRAS3 on ERK/AKT activity and reduced DIRAS3-mediated TFEB or FOXo3a nuclear localization and MAPLC3B expression in ovarian cancer cells.
LDFRT reverses cisplatin resistance of SKOV3/DDP cells possibly by upregulating the expression of FOXO3a and its downstream target PUMA, suggesting that LDFRT might be a potent chemosensitizer for the treatment of ovarian cancer.
Thus, our findings suggested that miR-498 acted as a new tumor suppressor by targeting the FOXO3 gene and inhibiting cell proliferation of ovarian cancer.
Here we describe the results of transcriptional profiles that identify the loss of the tumor suppressive transcription factor FOXO3a in a vast majority of high-grade serous ovarian carcinomas.
We found that high-grade serous ovarian carcinoma had significantly higher MIR182 (P=0.0003) and HMGA2 (P=0.04) expression, and significantly lower BRCA1 (P<0.0001) and FOXO3 (P<0.001) expression than normal controls.
Furthermore, combined siRNAs of Mirk with FoxO1 and/or FoxO3A led to fewer apoptotic cells and cisplatin sensitivity compared to Mirk siRNA alone, suggesting that FoxO is involved in Mirk-mediated cell survival and chemosensitivity of ovarian cancer.