CircMAST1 inhibits cervical cancer progression by hindering the N4-acetylcytidine modification of YAP mRNA.

BACKGROUND: Cervical cancer (CCa) is the fourth most common cancer among females, with high incidence and mortality rates. Circular RNAs (circRNAs) are key regulators of various biological processes in cancer. However, the biological role of circRNAs in cervical cancer (CCa) remains largely unknown. This study aimed to elucidate the role of circMAST1 in CCa. METHODS: CircRNAs related to CCa progression were identified via a circRNA microarray. The relationship between circMAST1 levels and clinicopathological features of CCa was evaluated using the clinical specimens and data of 131 patients with CCa. In vivo and in vitro experiments, including xenograft animal models, cell proliferation assay, transwell assay, RNA pull-down assay, whole-transcriptome sequencing, RIP assay, and RNA-FISH, were performed to investigate the effects of circMAST1 on the malignant behavior of CCa. RESULTS: CircMAST1 was significantly downregulated in CCa tissues, and low expression of CircMAST1 was correlated with a poor prognosis. Moreover, our results demonstrated that circMAST1 inhibited tumor growth and lymph node metastasis of CCa. Mechanistically, circMAST1 competitively sequestered N-acetyltransferase 10 (NAT10) and hindered Yes-associated protein (YAP) mRNA ac4C modification to promote its degradation and inhibit tumor progression in CCa. CONCLUSIONS: CircMAST1 plays a major suppressive role in the tumor growth and metastasis of CCa. In particular, circMAST1 can serve as a potential biomarker and novel target for CCa.

Patient-derived organoids as personalized avatars and a potential immunotherapy model in cervical cancer.

Cervical cancer remains a significant health issue in developing countries. However, finding a preclinical model that accurately reproduces tumor characteristics is challenging. Therefore, we established a patient-derived organoids (PDOs) biobank containing 67 cases of heterogeneous cervical cancer that mimic the histopathological and genomic characteristics of parental tumors. The in vitro response of the organoids indicated their ability to capture the radiological heterogeneity of the patients. To model individual responses to adoptive T cell therapy (ACT), we expanded tumor-infiltrating lymphocytes (TILs) ex vivo and co-cultured them with paired organoids. The PDOs-TILs co-culture system demonstrates clear responses that correspond to established immunotherapy efficiency markers like the proportion of CTLs. This study supports the potential of the PDOs platform to guide treatment in prospective interventional trials in cervical cancer.

CircVPRBP inhibits nodal metastasis of cervical cancer by impeding RACK1 O-GlcNAcylation and stability.

Lymph node (LN) metastasis is one of the most malignant clinical features in patients with cervical cancer (CCa). Understanding the mechanism of lymph node metastasis will provide treatment strategies for patients with CCa. Circular RNAs (circRNA) play a critical role in the development of human cancers. However, the role and mechanism of circRNAs in lymph node metastasis remain largely unknown. Here, it is reported that loss expression of circRNA circVPRBP was closely associated with LN metastasis and poor survival of CCa patients. In vitro and in vivo assays showed that circVPRBP overexpression notably inhibited lymphangiogenesis and LN metastasis, whereas RfxCas13d mediated silencing of circVPRBP promoted lymphangiogenesis and the ability of the cervical cancer cells to metastasize to the LNs. Mechanistically, circVPRBP could bind to RACK1 and shield the S122 O-GlcNAcylation site to promote RACK1 degradation, resulting in inhibition of Galectin-1 mediated lymphangiogenesis and LN metastasis in CCa. Taken together, the results demonstrate that circVPRBP is a potential prognostic biomarker and a novel therapeutic target for LN metastasis in CCa patients.

An Analysis on the Factors for Cervical Insufficiency Causing Adverse Emotions Among Pregnant Women at Different Gestation Phases.

Background: To analyze the anxiety, depression, and related factors among pregnant women with cervical insufficiency, so as to provide a reference for clinical psychological intervention as an adjuvant therapy. Methods: A total of 101 cases in China with cervical insufficiency were included in the observation group by a convenience sampling method, and 114 normal healthy women of childbearing age were selected as the control group. Participants were investigated and observed for anxiety and depression by SAS and SDS, respectively, to analyze the emotional state and influencing factors of the patients with cervical insufficiency. Stratified by the first, second and third trimesters, our study used whether depressive or not and whether anxiety or not as the dichotomous variables. A multivariate Logistic regression was adopted to analyze the influencing factors. Relevant influencing factors were screened out by the forward stepwise method in combination with professional knowledge and the number of variables. Results: There were statistical significant differences in SAS and SDS between observation group and control group and the incidence rate of anxiety and depression was higher in pregnant women with CI. Multivariate Logistic regression demonstrated that history of abnormal pregnancy was the main influencing factor for anxiety and depression in the early and middle gestation phases, and cervical insufficiency was the factor influencing the anxiety in early gestation and both anxiety and depression in the late gestation phase. Conclusion: Cervical insufficiency may have a negative impact on the emotions of pregnant women. Individualized and targeted mental care should be added into clinic work to prevent negative outcomes.

Roles of Pyroptosis-Related Gene Signature in Prediction of Endometrial Cancer Outcomes.

Endometrial cancer (EC) is one of the most common gynecological malignancies in women, accompanied by the increasing incidence and decreasing age of onset. Pyroptosis plays an important role in the occurrence and development of malignant tumors. However, the relationship between pyroptosis-related genes and tumor prognosis remains unclear. In this study, analyzing the expression levels and survival data of 33 pyroptosis-related genes in the Cancer Genome Atlas (TCGA) between normal samples and tumor samples, we obtained six pyroptosis-related prognostic differentially expressed genes (DEGs). Then, through the least absolute shrinkage and selection operator (LASSO) regression analysis, a gene signature composed of six genes (GPX4, GSDMD, GSDME, IL6, NOD2 and PYCARD) was constructed and divided patients into high- and low-risk groups. Subsequently, Kaplan-Meier (KM) plot, receiver operating characteristic (ROC) curve and principal component analysis (PCA) in two cohorts demonstrated that the gene signature was an efficient independent prognostic indicator. The enrichment analysis and immune infiltration analysis indicated that the high-risk group generally has lower immune infiltrating cells and less active immune function. In short, we constructed and validated a pyroptosis-related gene signature to predict the prognosis of EC, which is correlated to immune infiltration and proposed to help the precise diagnosis and therapy of EC.

Downregulation of LNMAS orchestrates partial EMT and immune escape from macrophage phagocytosis to promote lymph node metastasis of cervical cancer.

Epithelial-mesenchymal transition (EMT) is an essential step to drive the metastatic cascade to lymph nodes (LNs) in cervical cancer cells. However, few of them metastasize successfully partially due to increased susceptibility to immunosurveillance conferred by EMT. The precise mechanisms of cancer cells orchestrate EMT and immune evasion remain largely unexplored. In this study, we identified a lncRNA termed lymph node metastasis associated suppressor (LNMAS), which was downregulated in LN-positive cervical cancer patients and correlated with LN metastasis and prognosis. Functionally, LNMAS suppressed cervical cancer cells metastasis in vitro and in vivo. Mechanistically, LNMAS exerts its metastasis suppressive activity by competitively interacting with HMGB1 and abrogating the chromatin accessibility of TWIST1 and STC1, inhibiting TWIST1-mediated partial EMT and STC1-dependent immune escape from macrophage phagocytosis. We further demonstrated that the CpG sites in the promoter region of LNMAS was hypermethylated and contributed to the downregulation of LNMAS. Taken together, our results reveal the essential role of LNMAS in the LN metastasis of cervical cancer and provide mechanistic insights into the regulation of LNMAS in EMT and immune evasion.

Quality of life in patients with endometrial carcinoma: A Longitudinal Study.

AIM: To investigate the quality of life in patients with endometrial carcinoma and provide theoretical basis for nursing care. DESIGN: In this study, 69 patients diagnosed with endometrial carcinoma from 2016-2018 were included in the cohort. METHODS: Sixty-nine patients from our hospital who underwent endometrial cancer surgeries were selected. The SF-36 was used to investigate and analyse the patients' quality of life in the first, second and third months after their operations. Questionnaires were administered to analyse the factors affecting postoperative quality of life. RESULTS: Quality of life for the second and third months was obviously better than that for the first month after the operation (p < .05). Based on multivariate regression analysis, we found that patients with higher family income had better quality of life after surgery(p < .05). These results can provide some guidance for daily nursing work after endometrial cancer operation.

Circular RNA hsa_circ_0043280 inhibits cervical cancer tumor growth and metastasis via miR-203a-3p/PAQR3 axis.

Circular RNAs (circRNAs) are known to act as key regulators in a variety of malignancies. However, the role of circRNAs in cervical cancer (CCa) remains largely unknown. Herein, we demonstrated that a circRNA derived from the TADA2A gene (hsa_circ_0043280) was significantly downregulated in CCa and that this reduction in expression was correlated with a poor prognosis. Furthermore, our results demonstrated that hsa_circ_0043280 functions as a tumor suppressor to inhibit tumor growth and metastasis in CCa. Mechanistically, hsa_circ_0043280 competitively sponges miR-203a-3p and prevents miR-203a-3p from reducing the levels of PAQR3. Collectively, our results demonstrate that hsa_circ_0043280 plays a pivotal role in the development and metastasis of CCa, thus suggesting that hsa_circ_0043280 has significant potential as a prognostic biomarker and a therapeutic target for CCa.

TAB2 Promotes the Stemness and Biological Functions of Cervical Squamous Cell Carcinoma Cells.

Cancer stem cells are a key population participating in the promotion of the cervical cancer progression through interacting with cancer cells. Existing studies have preliminary revealed that cervical cancer stem cells contribute to tumor recurrence and chemotherapy resistance. However, the specific mechanisms involved in regulating cell functions remain largely unknown. Here, we analyzed published data from public databases and our global transcriptome data, thus identifying cancer-related signaling pathways and molecules. According to our findings, upregulated TAB2 was correlated to stem cell-like properties of cervical cancer. Immunohistochemistry staining of TAB2 in normal and cervical cancer tissues was performed. The cell function experiments demonstrated that knockdown of TAB2 reduced the stemness of cervical cancer cells and, importantly, prevented cervical cancer progression. Collectively, the therapeutic scheme targeting TAB2 may provide an option for overcoming tumor relapse and chemoresistance of cervical cancer via obstructing stemness maintenance.

High expression of PTPRM predicts poor prognosis and promotes tumor growth and lymph node metastasis in cervical cancer.

The prognosis for cervical cancer (CCa) patients with lymph node metastasis (LNM) is dismal. Elucidation of the molecular mechanisms underlying LNM may provide clinical therapeutic strategies for CCa patients with LNM. However, the precise mechanism of LNM in CCa remains unclear. Herein, we demonstrated that protein tyrosine phosphatase receptor type M (PTPRM), identified from TCGA dataset, was markedly upregulated in CCa with LNM and correlated with LNM. Moreover, PTPRM was an independent prognostic factor of CCa patients in multivariate Cox's proportional hazards model analysis and associated with poor prognosis. Furthermore, through gain-of-function and loss-of-function approaches, we found that PTPRM promoted CCa cells proliferation, migration, invasion, lymphangiogenesis, and LNM. Mechanistically, PTPRM promoted epithelial-mesenchymal transition (EMT) via Src-AKT signaling pathway and induced lymphangiogenesis in a VEGF-C dependent manner, resulting in LNM of CCa. Importantly, knockdown of PTPRM dramatically reduced LNM in vivo, suggesting that PTPRM plays an important role in the LNM of CCa. Taken together, our findings uncover a novel molecular mechanism in the LNM of CCa and identify PTPRM as a novel prognostic factor and potential therapeutic target for LNM in CCa.