LINC00665 enhances tumorigenicity of endometrial carcinoma by interacting with high mobility group AT-hook 1.

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.

Metapristone (RU486-derivative) inhibits endometrial cancer cell progress through regulating miR-492/Klf5/Nrf1 axis.

BACKGROUND: Endometrial cancer is an invasive gynecological cancer prevalent in the world. The pathogenesis of endometrial cancer is related to multiple levels of regulation, referring to oestrogen, tumor-suppressor gene (e.g. PTEN) or microRNAs (e.g. miR-23a and miR-29b). Metapristone is a hormone-related drug, which is widely used in clinical treatment of endometrial cancer. However, the underlying regulatory mechanism of metapristone on endometrial cancer is still unclear, especially the regulatory effect on microRNAs. The aim of this study is to investigate the specific molecular mechanism of metapristone regulating microRNAs in the treatment of endometrial cancer. METHODS: RL95-2 cells and Ishikawa cells were used as the endometrial cancer 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. The cell cancer model and mice cancer model were used to confirm the function and mechanism of metapristone affected on endometrial cancer in vitro and in vivo. Mechanically, cell proliferation was monitored using MTT assay, cell colony formation assay and EdU assay. Luciferase reporter assay was used to identify the downstream target gene of miR-492. 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 drug 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 decreasing the expression of miR-492 and its downstream target genes (Klf5 and Nrf1), which provided the theoretical basis in clinical treatment of endometrial cancer.

Circ_0067835 sponges miR-324-5p to induce HMGA1 expression in endometrial carcinoma cells.

Endometrial cancer is a common gynaecological malignant tumour among women across the world. Circular RNAs (circRNAs) are a novel kind of non-coding RNAs, and they can play a crucial role in multiple cancers. Nevertheless, the mechanisms of circRNAs in regulating gene expression in endometrial cancer are still unclear. Here, our work sought to focus on the role that circ_0067835 exert in progression and development of endometrial cancer cells. We observed circ_0067835 was markedly elevated in endometrial cancer. Then, changes in endometrial cancer cell (RL95-2 and HEC-1B) function were determined after circ_0067835 knockdown. Loss-of-functional assays revealed that circ_0067835 down-regulation significantly repressed RL95-1 and HEC-1B cell proliferation, migration and invasion. Bioinformatics analysis, luciferase reporter experiment and RNA pull-down assay were employed to predict and validate circ_0067835 can bind to miR-324-5p. Increase in miR-324-5p remarkably depressed the proliferation, migration and invasion of endometrial cancer cells via inhibiting high mobility group A1 (HMGA1). HMGA1 is identified as a vital prognostic biomarker in endometrial cancer. Currently, we reported circ_0067835 was positively correlated with HMGA1 in endometrial cancer. We implied that circ_0067835 was capable of sponging miR-324-5p and inducing its downstream target HMGA1 in vitro and in vivo. In conclusion, circ_0067835 can compete with miR-324-5p, resulting in HMGA1 up-regulation, and therefore induce the development of endometrial cancer.

Propranolol in the Treatment of Infantile Hemangiomas: A Meta-Analysis in Chinese Patients.

A meta-analysis was conducted to evaluate the efficacy of propranolol in the treatment of infantile hemangiomas (IHs) in Chinese infants. A statistically significant difference was found between infants treated using propranolol and those treated using corticosteroids (p < 0.001). The total effect pooled from 26 single-arm studies using meta-analysis of propranolol on IHs in Chinese infants was 93% (95% confidence interval 0.88, 0.96).

First-principles study of hydrogen sulfide decomposition on Sc-Ti3C2O2 single-atom catalyst.

CONTEXT: Hydrogen sulfide gas poses significant risks to both human health and the environment, with the potential to induce respiratory and neurological effects, and a heightened fatality risk at elevated concentrations. This article investigates the catalytic decomposition of H2S on a Sc-Ti3C2O2 single-atom catalyst(SAC) using the density functional theory-based first-principles calculation approach. Initially, the adsorption behavior of H2S on Ti3C2O2-MXene was examined, revealing weak physical adsorption between them. Subsequently, the transition metal atom Sc was introduced to the Ti3C2O2 surface, and its stability was studied, demonstrating high stability. Further exploration of H2S adsorption on Sc-Ti3C2O2 revealed direct dissociation of H2S gas molecules into HS* and H*, with HS* binding to Sc and H* binding to O on the Ti3C2O2 surface, resulting in OH groups. Using the transition state search method, the dissociation of H2S molecules on the SAC's surface was investigated, revealing a potential barrier of 2.45 eV for HS* dissociation. This indicates that the H2S molecule can be dissociated into H2 and S with the action of the Sc-Ti3C2O2 SAC. Moreover, the S atom left on the catalyst surface can aggregate to produce elemental S8, desorbing on the catalyst surface, completing the catalytic cycle. Consequently, the Sc-Ti3C2O2 SAC is poised to be an efficient catalyst for the catalytic decomposition of H2S. METHODS: The Dmol3 module in Materials Studio software based on density functional theory is used in this study. The generalized gradient approximation method GGA-PBE is used for the exchange-correlation function. The complete LST/QST and the NEB methods in the Dmol3 module were used to study the minimum energy path of the dissociation of hydrogen sulfide molecules on the catalyst surface.

Deciphering lung granulomas in HIV & TB co-infection: unveiling macrophages aggregation with IL6R/STAT3 activation.

Tuberculosis (TB) remains a leading cause of mortality among individuals coinfected with HIV, characterized by progressive pulmonary inflammation. Despite TB's hallmark being focal granulomatous lung lesions, our understanding of the histopathological features and regulation of inflammation in HIV & TB coinfection remains incomplete. In this study, we aimed to elucidate these histopathological features through an immunohistochemistry analysis of HIV & TB co-infected and TB patients, revealing marked differences. Notably, HIV & TB granulomas exhibited aggregation of CD68 + macrophage (Mφ), while TB lesions predominantly featured aggregation of CD20+ B cells, highlighting distinct immune responses in coinfection. Spatial transcriptome profiling further elucidated CD68+ Mφ aggregation in HIV & TB, accompanied by activation of IL6 pathway, potentially exacerbating inflammation. Through multiplex immunostaining, we validated two granuloma types in HIV & TB versus three in TB, distinguished by cell architecture. Remarkably, in the two types of HIV & TB granulomas, CD68 + Mφ highly co-expressed IL6R/pSTAT3, contrasting TB granulomas' high IFNGRA/SOCS3 expression, indicating different signaling pathways at play. Thus, activation of IL6 pathway may intensify inflammation in HIV & TB-lungs, while SOCS3-enriched immune microenvironment suppresses IL6-induced over-inflammation in TB. These findings provide crucial insights into HIV & TB granuloma formation, shedding light on potential therapeutic targets, particularly for granulomatous pulmonary under HIV & TB co-infection. Our study emphasizes the importance of a comprehensive understanding of the immunopathogenesis of HIV & TB coinfection and suggests potential avenues for targeting IL6 signaling with SOCS3 activators or anti-IL6R agents to mitigate lung inflammation in HIV & TB coinfected individuals.

2023: A year of accomplishments for the 13 Science Citation Index Expanded- and Emerging Sources Citation Index-indexed Baishideng journals.

In 2023, Baishideng Publishing Group (Baishideng) routinely published 47 open-access journals, including 46 English-language journals and 1 Chinese-language journal. Our successes were accomplished through the collective dedicated efforts of Baishideng staffs, Editorial Board Members, and Peer Reviewers. Among these 47 Baishideng journals, 7 are included in the Science Citation Index Expanded (SCIE) and 6 in the Emerging Sources Citation Index (ESCI). With the support of Baishideng authors, company staffs, Editorial Board Members, and Peer Reviewers, the publication work of 2023 is about to be successfully completed. This editorial summarizes the 2023 activities and accomplishments of the 13 SCIE- and ESCI-indexed Baishideng journals, outlines the Baishideng publishing policy changes and additions made this year, and highlights the unique advantages of Baishideng journals.

Risk factors for mitral valve dysfunction, reoperation and death following repair of the primary mitral valve disease in children.

Background: After primary mitral valve (MV) repair, residual mitral valve regurgitation (MR) and recurred mitral valve stenosis (MS) are the principal occurrences. This study's purpose is to identify the risk factors of MV dysfunction, reoperation and death following repair of primary MV diseases. Methods: We retrospectively reviewed 98 patients (47 males and 51 females) with primary MV diseases between January 2013 and December 2021. The median age was 34 months [interquartile range (IQR), 11.4-59] for male and 24 months (IQR, 7.35-72) for female. The left ventricular ejection fraction (LVEF), the left ventricular end-diastolic volume index (LVEDVI) and left ventricular end-systolic volume index (LVESVI) were assessed to evaluate patient's left ventricular function. Risk factors that increased the likelihood of MV dysfunction, reoperation and death after surgery were investigated. Results: During the 23.5 months (IQR, 9-44.5) of follow-up, 5 (5.1%) patients died, including one early death and two late deaths (n=3; 3.9%) in the MR group and one early death and one late death (n=2; 9.1%) in the MS group. Seven (9.2%) patients in the primary MR disease group and 2 (9.1%) patients in the primary MS disease group required a second MV operation for a total reoperation rate of 9.2% (9/98). As of the most recent follow-up, 34 patients experienced MV dysfunction. No significant difference was recorded between primary MR and MS disease groups in Kaplan-Meier freedom from MV dysfunction and reoperation. Mixed MV pathology (P=0.014) acted as an independent risk factor for MV dysfunction, and ≥ moderate MR at 24 h after first surgery (P=0.014) an independent risk factor for MV reoperation. Double-orifice MV technique (P=0.002), MV reoperation (P=0.023) and severe MR at 24 h after first surgery (P=0.028) were independent risk factors for death. Conclusions: The Kaplan-Meier freedom from MV dysfunction and reoperation were comparable between primary MR and MS disease groups. A high probability of MV dysfunction was predicted due to the mixed MV pathology. Patients with ≥ moderate MR at 24 h after first surgery had a higher risk of MV reoperation. Double-orifice MV technique, MV reoperation and severe MR at 24 h after first surgery had a higher risk for death.

Cell sheet-basedin vitrobone defect model for long term evaluation of bone repair materials.

Development of tissue-engineeredin vitrohuman bone defect models for evaluation of bone repair materials (BRMs) is a promising approach for addressing both translational and ethical concerns regarding animal models. In this study, human bone marrow mesenchymal stem cell sheets were stacked to form a periosteum like tissue. HE staining showed a cell-dense, multilayered structure. BRMs were implanted in the defect area of the three-dimensional (3D) model. The CCK-8 test demonstrated that the 3D model was stronger in resisting the cytotoxicity of three kinds of commercial BRMs than the 2D culture model, which was consistent within vivoresults. After 28 d implantation in the 3D model, western blot and RT-qPCR showed that three materials induced increased expressions of RUNX2, OSX, OCN, OPN, while Materials B and C seemed to have stronger osteoinductivity than A.In vivoexperiments also confirmed the osteoinductivity of the BRMs after 28 and 182 d implantation. Alizarin red staining proved that the mineralized nodules of Materials B and C were more than that of A. The differences of osteogenic properties among three BMRs might be attributed to calcium ion release. This cell sheet-based bone tissue model can resist cytotoxicity of BRMs, demonstrating the priority of long-term evaluation of osteoinductivity of BRMs. Further, the osteoinduction results of the 3D model corresponded to that ofin vivoexperiments, suggesting this model may have a potential to be used as a novel tool for rapid, accurate evaluation of BRMs, and thus shorten their research and development process.

Middle to long-term outcomes of surgical repair for atrioventricular septal defect: a single-center study.

Background: The exact incidence and predictors of mortality and left atrioventricular valve (LAVV) re-operation in congenital atrioventricular septal defect (AVSD) repair are still unclear. This study analyzed the middle to long-term outcomes of surgical repair for AVSD. Methods: A total of 150 patients (69 males and 81 females) who underwent AVSD repair at Children's Hospital of Fudan University from January 2013 to December 2021 were divided into complete defect group (C-group, 67 cases), transitional defect group (T-group, 26 cases), and partial defect group (P-group, 57 cases). Outcomes during the peri-operative and 10-year follow-up periods were evaluated. Results: The total mortality was 5.33% (8/150), including seven early deaths (10.4%) and no late deaths in the C-group, no early deaths (0%) and one late death (1.8%) in the P-group, and no early or late deaths in the T-group. Up to the last follow-up, severe LAVV regurgitation had occurred in 27 patients, including 16 in the C-group, four in the T-group, and seven in the P-group. In total, 12 (12/150, 8.0%) patients received LAVV re-operation, including seven in the C-group, three in the T-group, and two in the P-group. Cox regression analysis showed that pre-operative severe pulmonary hypertension (P=0.006) and severe LAVV regurgitation within 24 hours after the first surgery (P=0.023) were independent risk factors for mortality. ≥ Moderate LAVV regurgitation within the first 24 hours after surgery (P=0.014) was an independent risk factor for LAVV re-operation. Conclusions: Complete AVSD repair increased the risk of early death, severe LAVV regurgitation and re-operation. Pre-operative severe pulmonary hypertension and residual severe LAVV regurgitation indicated high risk for mortality. ≥ Moderate LAVV regurgitation within 24 hours after the first surgery predicted a high probability of LAVV re-operation.

Reciprocal regulation of CIP2A and AR expression in prostate cancer cells.

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein overexpressed in human malignancies, including prostate cancer (PCa). In this study, we aimed to explore the oncogenic function of CIP2A in PCa cells and its underlying mechanism. We showed that 63.3% (38/60 cases) of PCa tissues exhibited a high CIP2A immunostaining, compared to 25% (3/12 cases) of BPH samples (p = 0.023). Furthermore, the protein level of CIP2A was positively correlated with patients' short survival time and nuclear AR levels in PCa tissues. Compared to PZ-HPV-7, an immortalized prostate cell line, androgen-sensitive LNCaP C-33, androgen-independent LNCaP C-81, or 22Rv1 cells exhibited a high CIP2A level, associated with high protein and phosphorylation levels of AR. While AR expression and activity modulated CIP2A expression, manipulating CIP2A expression in PCa cells regulated their AR protein levels and proliferation. The reduction of CIP2A expression also enhanced the sensitivity of PCa cells toward Enzalutamide treatment. Our data further showed that depletion of polo-kinase 1 (PLK1) expression or activity in C-81 or 22Rv1 cells caused reduced protein levels of c-Myc and AR. Notably, inhibition of PLK1 activity could abolish CIP2A-promoted expressions in c-Myc, AR, and prostate-specific antigen (PSA) in C-33 cells under an androgen-deprived condition, suggesting the role of PLK1 activity in CIP2A-promoted AR expression. In summary, our data showed the existence of a novel regulation between CIP2A and AR protein levels, which is critical for promoting PCa malignancy. Thus, CIP2A could serve as a therapeutic target for PCa.

Dual inhibition of RNAi therapeutic miR-26a-5p targeting cMet and immunotherapy against EGFR in endometrial cancer treatment.

BACKGROUND: Precise prediction of drug combination targeting tumor cells effectively is a crucial challenge for tumor therapy, especially for endometrial cancer (EC). Considering the resistance, crosstalk that occurs between the receptor tyrosine kinase mesenchymal-epithelial transition factor (cMet) and epidermal growth factor receptor (EGFR), and their indispensable influence on the occurrence of EC, this study aimed to explore a novel therapeutic approach for EC treatment through blocking cMet and EGFR simultaneously. METHODS: In the present study, the expression of miR-26a-5p in EC cell lines was detected using quantitative real-time polymerase chain reaction assay. The potential role of miR-26a-5p in the development of EC was examined using cell counting kit assay, 5-ethynyl-2'- deoxyuridine staining, wound healing assay, and cell apoptosis staining assay. Subsequently, the effect of upregulated miR-26a-5p in vivo was confirmed on a xenograft model. Luciferase reporter assay and Western blot analysis were performed to verify the relation between miR-26a-5p and cMet. Furthermore, the dual therapeutic effect of miR-26a-5p and EGFR monoclonal antibody cetuximab was confirmed in vivo and in vitro. RESULTS: The results indicated that miR-26a-5p expression significantly reduced in EC cell lines compared with the normal endometrial cell line. Furthermore, the overexpression of miR-26a-5p inhibited the progression of EC, including cell migration, cell proliferation, and cell apoptosis in vivo and in vitro. Subsequently, mir-26a-5p regulated the expression of cMet and the downstream the hepatocyte growth factor (HGF)/cMet pathway, thus exerting an inhibitory effect on EC cells. In addition, the study also demonstrated that the upregulation of miR-26a-5p could significantly enhance the inhibitory effect of cetuximab compared with the use of cetuximab alone in vivo and in vitro. CONCLUSIONS: RNAi therapeutic miR-26a-5p suppressed the progression of EC through regulating the cMet/HGF pathway. The dual therapy using RNA interference and neutralizing antibody simultaneously blocked tumor targets, including cMet and EGFR, thus providing a novel approach for overcoming the resistance to the inhibitors against a single target in EC treatment.

lncRNA OIP5-AS1 Suppresses Cell Proliferation and Invasion of Endometrial Cancer by Regulating PTEN/AKT via Sponging miR-200c-3p.

BACKGROUND: Endometrial carcinoma (EC) is one of the major gynecologic malignancy cancers affecting females with dismal prognosis and high mortality around the world. Numerous studies have proven that an aberrant level of long noncoding RNAs is present in many endometrial cancer patients, while the underlying molecular mechanism remains unclear. METHOD: The expression levels of lncRNA OIP5-AS1, miR200c-3p, and PTEN were measured by a quantitative real-time polymerase chain reaction in endometrial cancer tissue and endometrial cancer cells. CCK8 assay, wound-healing assay, and cell colony formation were applied to evaluate cell proliferation, cell migration, and cell colony formation ability. Cell cycle and cell apoptosis were detected by flow cytometry. The interactions between OIP5-AS1, miR200c-3p, and PTEN were explored by luciferase activity. RESULTS: In the present study, we demonstrated that long noncoding RNA OIP5-AS1 was significantly reduced in EC tissue compared with normal tissue. The lower expression level of OIP5-AS1 was also confirmed in four kinds of EC cell lines compared with the normal endometrial cell line. Gain- and loss-of-function of experiments indicated that upregulation of OIP5-AS1 could inhibit the proliferation, migration, and invasion of EC cells in vitro. Meanwhile, overexpression of OIP5-AS1 could also suppress the growth of tumor in the xenograft model. Moreover, further study revealed that miR-200c-3p could bind to OIP5-AS1, and the loss function of miR-200c-3p could reverse the elevated OIP5-AS1's inhibitory effect on the progression of EC. Furthermore, we found that downregulation of miR-200c-3p was inversely correlated with PTEN expression in EC cells. Reduced OIP5-AS1 could lead to the accumulation of miR-200c-3p, which could induce the upregulation of PTEN indirectly. CONCLUSION: Our study demonstrated a novel molecular mechanism that lncRNA OIP5-AS1 could modulate the progression of EC by combining competitively with miR-200c-3p to control the PTEN/AKT pathway in EC cells, which might supply important information for developing novel therapeutic strategies for EC patients.

Inhibition of Lnc-OC1 Induced Cell Apoptosis and Decreased Cell Viability by Releasing miR-34a and Inhibiting PD-L1 in Endometrial Carcinoma.

Now, there is a growing awareness of the role to long non-coding RNAs (lncRNAs) in tumorigenesis and progression of a variety of malignancies including endometrial carcinoma (EC). Here, we explored the potential molecular mechanism of Lnc-OC1, a novel lncRNA, in the development of EC. Our results suggested that Lnc-OC1 was significantly upregulated in EC tissues comparing with normal tissues. Besides, Lnc-OC1 was higher expressed in the more advanced stage of EC. Therefore, Lnc-OC1 might be a crucial regulator in the progress of EC. Moreover, knockdown of Lnc-OC1 leaded to an inhibition of cell viability and a raise of cell apoptosis. In addition, Lnc-OC1 could sponge miR-34a and thus decrease its expression. miR-34a was proved to be a tumor suppressor in different malignance, hence downregulating Lnc-OC1 helped to alleviate EC by releasing miR-34a. Furthermore, rescue experiments significantly indicated that knockdown of Lnc-OC1 inhibited cell growth through repressing PD-L1 expression at least partially. Concisely, our results proved that Lnc-OC1/miR-34a/PD-L1 axis might serve as a therapeutic target of EC.

circTNFRSF21, a newly identified circular RNA promotes endometrial carcinoma pathogenesis through regulating miR-1227-MAPK13/ATF2 axis.

BACKGROUND: Circular RNA is a type of non-coding RNA with great potential in regulating gene expression and associated with disease progression. However, the role of circular RNA in endometrial carcinoma (EC) remains largely unknown. RESULTS: In this study, we found that circTNFRSF21 was highly expressed in EC cells and tumor tissues. In vitro and in vivo results showed that circTNFRSF21 was linked to increased EC cell growth and EC xenografts formation in nude mice. Mechanically, we showed that circTNFRSF21 acts as a sponge of miR-1227 in EC cells to rescue MAPK13/ATF2 signaling pathway activity. CONCLUSIONS: Our studies suggested that in the EC, circTNFRSF21 promotes EC formation through downregulating miR-1227 expression and activating MAPK13/ATF2 signaling pathway. These findings provide strong evidence that circTNFRSF21-miR-1227-MAPK13/ATF2 axis is a promising target for EC treatment. METHODS: qRT-PCR was used to detect circTNFRSF21expression in EC patients and EC cell lines. Cell growth, cell colony formation, cell apoptosis, cell cycle progression, and in vivo tumor formation assays were used to evaluate the roles of circTNFRSF21 in EC. Western blot, luciferase assay, RNA pull-down, siRNA knockdown, and CRISPR gene knock out assays were applied to study the mechanisms through which circTNFRSF21 regulates EC formation.

Hsa_circ_0061140 promotes endometrial carcinoma progression via regulating miR-149-5p/STAT3.

Circular RNAs (circRNAs) are reported to participate in many diseases including tumorigenesis, which can modulate gene expression post-transcriptionally. Up to now, the detailed function of circRNAs in endometrial carcinoma (EC) progression are to be well established. hsa_circ_0061140 has been revealed to act as crucial regulators in several cancers. This current study was carried out to explore the function of hsa_circ_0061140 in EC development. Here, hsa_circ_0061140 expression was modulated using functional assays and we found loss of hsa_circ_0061140 significantly restrained EC cells progression. Moreover, we revealed hsa_circ_0061140 could act as a molecular sponge for miR-149-5p. STAT3 was predicted as a downstream target gene of miR-149-5p. As well known, miR-149-5p is reported to be involved in tumor growth and metastasis. Then, dual luciferase reporter experiment and RIP assay were carried out to evidence the direct binding association between hsa_circ_0061140 and miR-149-5p. miR-149-5p was able to negatively modulate STAT3 expression. Additionally, we proved hsa_circ_0061140 exhibited its oncogenic role due to the modulation of miR-149-5p and STAT3 axis. Taken these together, we suggested that hsa_circ_0061140 might act as an effective therapy to treat EC through functioning as a molecular sponge of miR-149-5p.

CD47 Enhances Cell Viability and Migration Ability but Inhibits Apoptosis in Endometrial Carcinoma Cells via the PI3K/Akt/mTOR Signaling Pathway.

Purposes: To measure expression levels of CD47 during endometrial carcinoma development, and to determine specific modulatory effects. Methods: CD47 expression levels in endometrial carcinoma tissues and adjacent tissues were analyzed using qRT-PCR. CD47-overexpressed or downregulated cell models were established using CD47 plasmid or CD47 shRNA. The effects of CD47 on HEC-1A and Ishikawa cell growth were evaluated using CCK-8 assays. Migration ability of transfected HEC-1A and Ishikawa cells were examined using wound healing assays. Flow cytometry was used to measure the effects of CD47 on apoptosis and the cell cycle in HEC-1A and Ishikawa cells. Western blot was used to analyze the correlation between CD47 expression level and PI3K/Akt/mTOR signaling pathway. Results: Highly expressed CD47 was observed in endometrial carcinoma tissues, with higher levels in more advanced tissues than in early tissues. Upregulation of CD47 enhanced cell viability and migration ability in HEC-1A and Ishikawa cells, while silencing CD47 caused the opposite results. CD47 overexpression suppressed apoptosis and inhibited cell cycle arrest in HEC-1A and Ishikawa cells. CD47 upregulation contributes to the activation of PI3K/Akt/mTOR signaling pathway in endometrial carcinoma cells. Conclusion: CD47 exerts oncogenic functions in endometrial carcinoma by activating PI3K/Akt/mTOR signaling, suggesting it may be a novel immunotherapeutic target for therapeutic interventions.

Multi-omics profiling reveals distinct microenvironment characterization of endometrial cancer.

Endometrial cancer is a heterogeneous disease with distinct molecular characteristics, however, the current clinical trials in immunotherapies have reported only a 13% response rate in endometrial cancer. In this study, we aim to estimate the relative abundance of immune cells infiltrating into the tumor tissues. The samples were clustered based on the immune cell abundance. Most of cluster-specifically mutated genes were detected in clusters I and II, while the copy number alterations were specifically detected in cluster III. Overrepresentation enrichment analysis (ORA) of the genes specifically upregulated in a specific cluster revealed that the immune-related pathways were enriched by the genes in cluster I. Moreover, immune checkpoint proteins and immune co-stimulators were also observed to be highly expressed in cluster I. In addition, we also built a multivariable Cox regression model based on the immune checkpoint genes and co-stimulators. The high-risk and low-risk groups stratified by the risk scores of the Cox model exhibited significant prognostic difference in both training and validation datasets. In summary, the systematic analysis greatly improves our understanding of the immunophenotype of endometrial cancer and its association with biomarkers and prognosis.

[Investigation of selective inhibition of digoxin derivative on retinoic acid-related orphan nuclear receptor γt transcription activity using molecular docking].

OBJECTIVE: Psoriasis is an autoimmune-related chronic inflammatory skin disease strongly associated with the dysfunction of Th17 cells. Retinoic acid-related orphan nuclear receptor γt (RORγt) plays a critical role in the differentiation and maturation of Th17 cells and in cell-derived immunologic derangement. We conducted this study to investigate potential mechanism by which the derivative of digoxin selectively antagonizes RORγt transcriptional activity. METHOD: Using molecular docking in combination with molecular electrostatic potential (MEP), we detected the interaction between the derivative of digoxin (Dhd) and ROR transcription factor (RORα,RORß and RORγt), and the results were further confirmed by bioluminescent assay. RESULT: Molecular docking demonstrated that Dhd could exclusively inhibit the conformation of RORγt; bioluminescent assay further indicated that RORγt was selectively antagonized by Dhd in a dose- and time-dependent manner. CONCLUSION: Dhd can selectively suppress RORγt transcriptional activity.

[Investigation of micro-aqueous covalent immobilization of horseradish peroxidase by "conformation memory"].

We has studied the feasibility of preventing protein from denature during covalent immobilization by "conformation memory", which was achieved by freeze-drying under enzyme active conformation and cross-linked with carrier under micro-aqueous media (MAM). Horseradish peroxidase (HRP) and chitosan beads have been used as the model enzyme and carrier. The MAM consisted of 99% dioxane and 1% water. We compared the immobilized HRP under MAM with that under traditional aqueous solvent, found that the optimum temperature of both was raised to 60 degrees C, and the optimum pH was 6.5. However, the MAM-immobilized HRP had shown less activity loss during usage and six times higher activity than that immobilized under aqueous solvent. After 30 min incubation at 70 degrees C, the MAM-immobilized HRP remained 75.42% activity while the aqueous-media-immobilized enzyme only 15.4%. The MAM-immobilized HRP has shown a better operation stability with 77.69% residue activity after 5 times of repeat operation while the aqueous-media-immobilized enzyme only 16.67%. In addition, the MAM-immobilized HRP had also shown more advantages when used in phenol removal. We constructed enzyme electrodes (CS-HRP-SWCNTs/Au) to further display the different properties of the two immobilized HRP. MAM-immobilized HRP-electrode has shown two times stronger response signal to H2O2 than that immobilized under aqueous media, which indicated a better enzyme activity of MAM-immobilized HRP. Our research demonstrated that the conformation memory, to some extent, did contribute to preventing protein from denaturing when use HRP as a model, and it is feasible to immobilize enzyme by covalent cross-linking method under micro-aqueous media.