Background: Endometrial cancer is the prevalent invasive gynecological cancer in the world. The pathogenesis of endometrial cancer involves many signaling pathways which are related with oestrogen, tumor-suppressor gene (e.g. PTEN) or microRNAs (e.g. miR-23a and miR-29b). Metapristone is a hormone-related drug and widely used in endometrial cancer clinical therapeutics. However, the deep regulatory mechanism of metapristone to endometrial cancer is not clear, especially the relationship with microRNAs. In this research, we aimed to figure out the specific molecular mechanism on the regulation of metapristone to microRNAs during the treatment of endometrial cancer.Methods: RL95-2 cells and Ishikawa cells were used as the endometrial cancer cell models. MiR-492 or si-miR-492 was transfected into RL95-2 cells and Ishikawa cells to explore the role of miR-492 in endometrial cancer. Moreover, the mice tumor model was used to confirm the function of metapristone and the regulating process by miR-492/Klf5/Nrf1 axis in vivo. Mechanically, cell proliferation was monitored using the MTT assay, cell colony formation assay and EdU assay. Luciferase reporter assay was used to identify the downstream target gene of miR492. The protein expression and RNA expression were respectively measured by western blot and qRT-PCR for cell signaling pathway research, subsequently, were verified in the mice tumor model via immunohistochemistry.Results: Metapristone as a kind of hormone-related drugs significantly inhibited the endometrial cancer cell growth through regulating cell apoptosis-related gene expression. Mechanically, miR-492 and its target genes Klf5 and Nrf1 were highly expressed in the endometrial cancer cell lines, which promoted cell proliferation and inhibited cell apoptosis. Metapristone decreased the expression of miR-492 and its target genes Klf5 and Nrf1, leading to endometrial cancer cell growth inhibition in vitro and in vivo.Conclusion: Metapristone inhibited the endometrial cancer cell growth through regulating the cell apoptosis-related signaling pathway and inhibiting the expression of miR-492 and its downstream target genes (Klf5 and Nrf1), which provided the theoretical basis of endometrial cancer in clinical treatment.

Background: Endometrial cancer is the prevalent invasive gynecological cancer in the world. The pathogenesis of endometrial cancer involves many signaling pathways which are related with transcription factors or microRNAs. Metapristone is a hormone related drug and widely used in endometrial cancer clinical therapeutics. However, the deep regulatory mechanism of metapristone is not clear. In this research, we aimed to figure out the specific molecular mechanism during the treatment of endometrial cancer with metapristone.Methods: In this study, RL95-2 cells and Ishikawa cells were used as the endometrial cancer cell models. miR-492 was transfected into RL95-2 cells and Ishikawa cells. The miRNA expression was measured by qRT-PCR. Moreover, the mice tumor model was used to confirm the function of metapristone and the regulating process by miR-492/Klf5/Nrf1 axis in vivo. The protein expression was measured by western blot. Cell proliferation and apoptosis was monitored using the MTT assay, cell colony formation assay and EdU assay.Results: Firstly, the results indicated that metapristone as a kind of hormone-related drugs could significantly inhibit the endometrial cancer cell growth through regulating cell apoptosis-related gene expression. Meanwhile, miR-492 was detected to be highly expressed in the endometrial cancer cell lines. Overexpression of miR-492 could promote the cell proliferation and inhibit the cell apoptosis. Furthermore, the results demonstrated that the downstream target genes of miR-492 were Klf5 and Nrf1, which were inhibited by metapristone. At the animal level, metapristone also inhibited the endometrial cancer cell growth through down-regulating the expression of miR-492 and decreasing the protein level of Klf5 and Nrf1. Conclusion: Taken together, this study indicated that metapristone inhibited the endometrial cancer cell growth through regulating the cell apoptosis related signaling pathway and the expression of miR-492 and its downstream target genes (Klf5 and Nrf1), which provided the theoretical basis of endometrial cancer in clinical treatment.

Background: Endometrial carcinoma is a frequently diagnosed cancer among females. LncRNAs are reported to be associated with various cancers. Their biological roles in endometrial carcinoma progression is an emerging scientific area. LINC00665 can exert a significant role in many cancers. However, its potential function in endometrial carcinoma is still poorly known.Method: qRT-PCR was carried out to test expression of LINC00665 and HMGA1. Western blot analysis was carried out to detect protein expression of HMGA1. Cell proliferation was evaluated using Cell Counting Kit-8 (CCK-8) and EdU assay. Flow cytometry assay was used to determine cell apoptosis and cell cycle. Wound healing and transwell invasion assay was carried out to test cell migration and invasion. Immunohistochemical staining and HE staining were conducted to assess Ki-67 and tumor growth respectively.Results: Expression of LINC00665 in clinical endometrial carcinoma tissues and cells was obviously up-regulated. Loss of LINC00665 could repress endometrial carcinoma cell viability, induce cell apoptosis and block cell cycle in G1 phase. KLE and HHUA cell migration and invasion ability were depressed by LINC00665 shRNA. Decrease of LINC00665 suppressed endometrial carcinoma tumorigenicity in vivo. RIP assay proved that LINC00665 directly bound with HMGA1 protein. shRNA of HMGA1 obviously restrained endometrial carcinoma cell growth and cell invasion.Conclusions: LINC00665 might promote endometrial carcinoma progression by positively modulating HMGA1.

Background: Endometrial cancer is one of the most common cancers affecting women's health. The pathogenesis of endometrial cancer involves many signaling pathways which are related with transcription factors or microRNAs. Recent studies have reported that endometrial cancer is also related with the sexual-mediated hormones. The purpose of this research is to treat the endometrial cancer with the hormone-related drugs, and find out the specific molecular mechanism. Methods: In this study, RL95-2 cells and Ishikawa cells were used as the endometrial cancer cell models. miR-492 was transfected into RL95-2 cells and Ishikawa cells. The miRNA expression was measured by qRT-PCR. The protein expression was measured by western blot. Cell proliferation was monitored using the MTT assay and cell colony formation assay. Cell apoptosis was monitored using EdU assay. Results: Firstly, the results indicated that metapristone as a kind of hormone-related drugs could significantly inhibit the endometrial cancer cell growth through regulating cell apoptosis-related gene expression. Meanwhile, miR-492 was detected to be highly expressed in the endometrial cancer cell lines. Overexpression of miR-492 could promote the cell proliferation and inhibit the cell apoptosis. Furthermore, the results demonstrated that the downstream target genes of miR-492 were Klf5 and Nrf1, which were inhibited by metapristone. At the animal level, metapristone also inhibited the endometrial cancer cell growth through down-regulating the expression of miR-492 and decreasing the protein level of Klf5 and Nrf1. Conclusion: Taken together, this study indicated that metapristone inhibited the endometrial cancer cell growth through regulating the cell apoptosis related signaling pathway and the expression of miR-492 and its downstream target genes (Klf5 and Nrf1), which provided the theoretical basis of endometrial cancer in clinical treatment.

Background: Endometrial carcinoma is a frequently diagnosed cancer among females. LncRNAs are reported to be associated with various cancers. Their biological roles in endometrial carcinoma progression is an emerging scientific area. LINC00665 can exert a significant role in many cancers. Up to now, its potential function in endometrial carcinoma is still poorly known.Method: qRT-PCR was carried out to test expression of LINC00665 and HMGA1. Western blot analysis was carried out to detect protein expression of HMGA1. Cell proliferation was evaluated using Cell Counting Kit-8 (CCK-8) and EdU assay. Flow cytometry assay was used to determine cell apoptosis and cell cycle. Would healing and transwell invasion assay was carried out to test cell migration and invasion. Immunohistochemical staining and HE staining were conducted to assess Ki-67 and tumor growth respectively.Results: Expression of LINC00665 in clinical endometrial carcinoma tissues and cells was obviously up-regulated. Loss of LINC00665 could repress endometrial carcinoma cell viability, induce cell apoptosis and blocked cell cycle in G1 phase. KLE and HHUA cell migration and invasion ability were depressed by LINC00665 shRNA. Decrease of LINC00665 suppressed endometrial carcinoma tumorigenicity in vivo. RIP assay evidenced LINC00665 directly bound with HMGA1 protein. shRNA of HMGA1 obviously restrained endometrial carcinoma cell growth and cell invasion.Conclusions: LINC00665 might promote endometrial carcinoma progression by positively modulating HMGA1.