Background: Mounting evidence indicates altered circadian rhythm represents a critical factor affecting carcinogenesis and tumor progression. The circadian gene neuronal PAS domain protein 2 (NPAS2) constitutes a newly discovered prognostic biomarker. NPAS2 dysregulation is found in multiple malignancies, although its functions in uterine corpus endometrial carcinoma (UCEC) remain largely unknown. Objective: To evaluate NPAS2's roles in UCEC and to explore the underlying mechanisms. Methods: NPAS2 transcription levels, patient prognosis, different clinical stages and target microRNAs in UCEC cases were comparatively assessed based on public databases, including UALCAN, GEPIA, TIMER, Kaplan-Meier plotter, starBase database, LinkedOmics and String. Then, qRT-PCR and immunohistochemical analysis were applied to analyze the expression of NPAS2 in UCEC tissue samples. CCK-8, clonogenic assay and flow cytometry were carried out for detecting cell viability, colony formation ability and cell apoptosis, respectively. Results: NPAS2 was upregulated in tissue samples from UCEC cases compared with the corresponding control specimens. NPAS2 overexpression was associated with decreased overall (OS), disease free (DFS) and relapse free (RFS) survival in UCEC. In addition, NPAS2 overexpression was associated with clinical stage, tumor grade, estrogen receptor status, myometrial invasion in UCEC. Furthermore, NPAS2 knockdown or overexpression altered cell proliferation and apoptosis in UCEC. Moreover, NPAS2 showed significant negative correlations with miR-17-5p and miR-93-5p, and positive correlations with miR-106a-5p and miR-381-3p in UCEC. Conclusion: NPAS2 overexpression is associated with poor prognosis and clinicopathological characteristics in UCEC and promotes proliferation and colony formation while inhibiting apoptosis. Finally, NPAS2 is associated with several miRNAs in UCEC.

Background: Preeclampsia (PE) is a serious obstetric complication. Recent studies point out that the functions of long intergenic noncoding RNA 00473 (linc00473), miR-424-5p, and Wnt/β-catenin signaling pathway were involved in the invasion and migration of extravillous trophoblast. Here, we investigated the role and mechanism of linc00473 in HTR-8/SVneo trophoblastic cell line and its role in PE. Method: The expression levels of linc00473 and miR-424-5p in placental tissues and the transfection efficiency of miR-424-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). HTR-8/SVneo cell invasion and proliferation were determined by transwell and Cell Counting Kit-8 (CCK-8) assays. The protein expressions of wnt3a, p-GSK3β, GSK3β, active β-catenin, and total β-catenin were detected by Western blot. The apoptosis and migration of HTR-8/SVneo cells were detected by flow cytometry and wound healing assays. The targeting relationships between linc00473, miR-424-5p, and wnt3a were predicted by ENCORI database and TargetScan V7.2 and were determined using dual-luciferase reporter assay.Results: The expression level of linc00473 was low and miR-424-5p was high in placenta of PE patients. Linc00473 can target miR-424-5p, while miR-424-5p target wnt3a. High expression of linc00473 and wnt3a promoted cell proliferation, migration, invasion, and inhibited cell apoptosis. However, miR-424-5p mimic inhibited HTR-8/SVneo cells proliferation, migration, invasion, while promoted cell apoptosis, partially reversed the effect of linc00473, while wnt3a overexpression partially counteracted the effect of miR-424-5p mimic. Conclusion: Linc00473 mediates the regulation of Wnt/β-catenin signaling pathway by miR-424-5p to affect the invasion and migration ability of trophoblastic cell line HTR-8/SVneo. It indicated that linc00473 is involved in PE and could be a therapeutic target.

c1q/TnF-α-related protein 9 (cTrP9) is downregulated in gestational diabetes mellitus (GdM) and may exert a protective effect against GdM, although its mechanism of action is yet to be elucidated. To investigate the specific role of cTrP9 in GdM, the human placental trophoblast cell line HTr8/SVneo was treated with high glucose (HG) to simulate the environment of GdM in vitro. The effects of cTrP9 on the HTr8/SVneo cells and endoplasmic reticulum (er) stress were analyzed before and after cTrP9 overexpression using reverse transcription-quantitative Pcr and western blotting. The results obtained demonstrated that cTrP9 alleviated er stress in the trophoblast cell line. after treating with the er-stress inducer tunicamycin, cell viability was investigated by performing cell counting Kit-8, Tunel and western blotting assays, which revealed that cTrP9 increased the activity of HTr8/SVneo cells induced by HG through the alleviation of er stress. Subsequently, eliSa and western blotting assay results demonstrated that cTrP9 inhibited HG-induced inflammation of the HTR8/SVneo cells by the reduction in ER stress. Finally, the detection of reactive oxygen species, nitric oxide (NO) synthase and NO levels confirmed that CTRP9 inhibited the oxidative stress of HTr8/SVneo cells induced by HG through the reduction of er stress. collectively, the results of the present study suggested that cTrP9 may decrease trophoblast cell damage caused by HG through the suppression of er stress, and therefore, cTrP9 may potentially be a therapeutic target in the treatment of GdM.

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Ovarian cancer is the leading and most common gynecological malignancy with high mortality, which greatly threatens women's life and health (Stewart et al., 2019;Webb & Jordan, 2017). Currently, surgery and chemoradiotherapy are the main treatment strategies for ovarian cancer, but patients still face risks of recurrence and drug resistance (Christie & Bowtell, 2017;Eisenhauer, 2017). Therefore, new therapeutic strategies need to be developed to improve the results of ovarian cancer patients.