We planned to investigate the possible influences of long non-coding RNA (opioid growth factor receptor pseudogene 1) OGFRP1 in endometrial cancer and its potential regulatory mechanism. We measured the level of OGFRP1 in endometrial cancer tissues and evaluated the influences of OGFRP1 dysregulation on the tumour cell biological processes of endometrial cancer cells. Further, the regulatory relationships between OGFRP1 and miR-124-3p, between miR-124-3p and Sirtuin1 (SIRT1) were, respectively, investigated. The interaction between OGFRP1 dysregulation and activation of PI3K/AKT/ GSK-3b pathway was revealed by Western blotting. OGFRP1 was up-regulated in endometrial cancer tissues and cells. OGFRP1 suppression inhibited the malignant behaviour (inhibited cell viability, promoted cell apoptosis, and suppressed cell migration and invasion) of the Ishikawa cells via negatively regulating miR-124-3p. SIRT1 was a target gene of miR-124-3p, and miR-124-3p regulated tumour growth and metastasis by the downstream signal of SIRT1. Moreover, suppression of OGFRP1 restrained the activation of PI3K/AKT/GSK-3b signals in the Ishikawa cells via miR-124-3p/SIRT1 axis. Our experiments revealed that upregulation of OGFRP1 may enhance the progression of endometrial cancer by regulating miR-124-3p/SIRT1 axis and by activating PI3K/AKT/GSK-3b pathway. OGFRP1 may be of significance in illustrating the biology of endometrial cancer.
Naringin is a promising anticancer bioflavonoid phytochemical, mainly extracted from citrus fruits. This study evaluates the antiproliferative effect and the cell death mechanism induced by naringin on cervical cancer (CC) cells. Our results demonstrated that naringin exerts significant inhibition in cell viability and exhibits IC50 value 745, 764, 793 µM against C33A, SiHa, and HeLa cells respectively. Annexin V FITC and immunoblotting analysis reveal significant apoptosis induction in cells exposed to higher doses naringin. Mechanistically, naringin induces endoplasmic reticulum (ER) stress-associated cell killing in CC cells. Naringin increases the protein expression of ER stress sensors, phosphorylates eIF2α by and activates apoptosis-associated protein CHOP and other associated proapoptotic proteins (PARP1 and caspase-3). Intriguingly, pre-treatment with of ER stress inhibitor (salubrinal), reverses the apoptotic effect exerted by naringin. Additionally, the naringin abrogates the β-catenin pathway by decreasing the protein expression as well as phosphorylation of β-catenin (Ser576) and GSK-3β (Ser9) and simultaneously triggers cell cycle arrest at a G0/G1 phase by increasing the expression of cell cycle checkpoint proteins p21/cip and p27/kip. Naringin induces ER stress-mediated apoptosis and simultaneously abrogates Wnt/β-catenin signaling which eventually triggers the arrest of the cell cycle at a G0/G1 phase in CC cells.
Wogonoside, a bioactive flavonoid component derived from Scutellaria baicalensis Georgi, has been reported to inhibit tumor growth in mice bearing various types of cancer cells such as breast cancer, lung cancer, and leukemia cells. However, whether wogonoside could inhibit tumor growth of endometrial cancer has not been elucidated. In this study, we explored the function of wogonoside on tumor growth and the underlying mechanism on endometrial cancer. Firstly, we investigated the effect of wogonoside on endometrial cancer cells and found that wogonoside could significantly decrease cell proliferation and metastasis. Mechanistically, wogonoside could aggravate the extent of ER stress and upregulate the phosphorylation level of Mammalian Ste20-like kinase 1, leading to the activation of the Hippo signaling pathway. Taken together, in vitro and in vivo data demonstrated that wogonoside could be a potent inducer of ER stress and could be further developed into a promising therapy for endometrial cancer.
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