BackgroundEndometrioid adenocarcinoma (EAC) is the most common subtype of endometrial cancer (EC) and is an estrogen-related cancer. In this study, we sought to investigate the expressions and mechanism of action of 17β-estradiol (E2) and long noncoding RNA (lncRNA) LINC01541 in G1/G2 EAC samples.MethodsThe expressions of estrogen receptor β (ESR2), LINC01541, miR-200s, and VEGFA were evaluated using real-time PCR in human EAC tissues (n = 8) and adjacent normal tissues (n = 8). Two EC cell lines (Ishikawa and RL95-2) were selected for validation in vitro. Bioinformatics analyses and luciferase reporter analyses were performed to verify potential binding sites. qRT-PCR, Western blot, and CCK-8 were used to identify the regulatory mechanisms of related genes in cell biological behavior.ResultsCompared with adjacent normal tissues, LINC01541 and miR-200s family (except miR-200c) were highly expressed in EAC tissues (n=8), while ESR2 and VEGFA were lowly expressed in EAC tissues (* P < 0.05; ** P < 0.01). In vitro: E2 inhibited the expression of LINC01541 and miR-429 in both cell lines, and estrogen antagonist (PHTPP) could reverse this effect, in addition, PHTPP could promote the proliferation of these two cancer cells, cell transfection LINC01541 also had this effect after overexpression of plasmid and miR-429 mimic. E2 promotes the expression of VEGFA in both cell lines, and PHTPP can also reverse this effect. LINC01541 interacts with miR-429 to promote the expression of each other, and both inhibit the synthesis of VEGFA in EAC cells after overexpression. Through the double validation of bioinformatics analysis and dual fluorescein reporter gene, it was confirmed that miR-429 targets the regulation of VEGFA expression (* P < 0.05; ** P < 0.01).ConclusionE2 promotes the synthesis of VEGFA by altering the expression levels of LINC01541 and miR-429 in EAC, thereby affecting the angiogenesis process of EAC. Also, E2-mediated LINC01541/miR-429 expression may affect cell migration in EAC. In addition, we identified a reciprocal promotion between LINC01541 and miR-429.

Objective: To investigate the effectiveness of ornidazole in inhibiting the progression of endometriosis in a rat model. Design: This was an in vivo experiment, including the ornidazole group (n=16) and the control group (n=14). Rats were provided with free access to water containing ornidazole (1 g/L) or drinking water only for 14 days. Materials and Methods: Surgical induction of endometriosis was performed in Sprague Dawley rats via autologous endometrial transplantation. Rats were provided with free access to water containing ornidazole (1 g/L) or drinking water only for 14 days. Once the rats were euthanized (ornidazole group, n=16; control group, n=14), histological signatures and the volumes of endometriosis lesions were assessed. Cells positive for the inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were counted. Angiogenesis was identified by assessing vascular endothelial growth factor (VEGF) and microvessel density. Results: The median lesion volume was lower in the ornidazole group (20.2 mm3; range, 5.7-53.3 mm3) than in the control group (81.25 mm3; range, 32.8-122.2 mm3; P = 0.007). Median IL-1β cell counts were 5.3 (range, 4.5-6.4) for ornidazole and 11.7 (range, 9.4-15.4) for control (P < 0.001). Mean IL-6 cell counts were 5.6 ± 1.8 for ornidazole and 11.3 ± 4.1 for control (P < 0.001). Median TNF-α cell counts were 5.7 (range, 4.5-7.2) for ornidazole and 12.1 (range, 10.0-15.9) for control (P < 0.001). Median VEGF cell counts were 8.1 (range, 6.5-11.4) for ornidazole and 18.3 (range, 14.2-21.0) for control (P = 0.001). Median microvessel density values were 11.3 (range, 7.7-21.8) for ornidazole and 28.7 (range, 13.1-48.2) for control (P = 0.012). Limitations: This study is a short period and small sample size experiment. In this study, multiple drug concentrations were not used. These findings are from a rat model of surgically induced endometriosis, and we did not evaluate the optimal dose of ornidazole or its hepatoxicity and nephrotoxicity in rats. We did not use in vitro models to assess the anti-inflammatory and antiangiogenic effects of ornidazole on endometriosis, and the specific anti-inflammatory and antiangiogenic mechanisms associated with ornidazole need to be further investigated. Conclusion: Ornidazole restricts the growth of endometriosis in rats, possibly by exerting anti-inflammatory and anti-angiogenesis effects.