BACKGROUND: Ovarian cancer poses a serious threat to women's health. Due to the difficulty of early detection, most patients are diagnosed with advanced-stage disease or peritoneal metastasis. We found that LncRNA MEG3 is a novel tumor suppressor, but its role in tumor occurrence and development is still unclear.; METHODS: We investigated the expression level of MEG3 in pan-cancer through bioinformatics analysis, especially in gynecological tumors. Function assays were used to detect the effect of MEG3 on the malignant phenotype of ovarian cancer. RIP, RNA pull-down, MeRIP-qPCR, actinomycin D test were carried out to explore the m6A methylation-mediated regulation on MEG3. Luciferase reporter gene assay, PCR and Western blot were implemented to reveal the potential mechanism of MEG3. We further confirmed the influence of MEG3 on tumor growth in vivo by orthotopic xenograft models and IHC assay.; RESULTS: In this study, we discovered that MEG3 was downregulated in various cancers, with the most apparent downregulation in ovarian cancer. MEG3 inhibited the proliferation, migration, and invasion of ovarian cancer cells. Overexpression of MEG3 suppressed the degradation of VASH1 by negatively regulating miR-885-5p, inhibiting the ovarian cancer malignant phenotype. Furthermore, we demonstrated that MEG3 was regulated at the posttranscriptional level. YTHDF2 facilitated MEG3 decay by recognizing METTL3‑mediated m6A modification. Compared with those injected with vector control cells, mice injected with MEG3 knockdown cells showed larger tumor volumes and faster growth rates.; CONCLUSION: We demonstrated that MEG3 is influenced by METTL3/YTHDF2 methylation and restrains ovarian cancer proliferation and metastasis by bindingmiR-885-5p to increase VASH1 expression. MEG3 is expected to become a therapeutic target for ovarian cancer. © 2024. The Author(s).

The function of Vasohibin-1 (VASH1) in human cancer has not been thoroughly or comprehensively examined. Here, we identified the tumor suppressor part of VASH1 across cancers, including epithelial ovarian tumors. Our study carefully contrasted the expression of VASH1 in pancancer and nontumorous tissues in a public database to explore its regulatory role in clinical prognosis, diagnosis, tumor purity, and immune cell infiltration. Next, we explored the antitumor mechanism of VASH1 through drug sensitivity, functional enrichment, and phenotypic experiments in ovarian cancer. Research suggests that the expression of VASH1 in neoplastic tissues is lower than that in normal tissues. VASH1 affects the OS and RFS of several tumor types. In addition, VASH1 expression resulted in a high OS and RFS in the diagnosis of tumor and nontumor tissues and negatively regulated tumor purity. Moreover, VASH1 controls the tumor microenvironment by regulating immunocyte infiltration. In ovarian cancer, VASH1 can serve as a biomarker to estimate the efficacy of chemotherapy. Functional enrichment analysis suggests that VASH1 plays a tumor suppressor role by regulating the extracellular matrix receptor pathway. VASH1 inhibition of the malignant phenotype of ovarian cancer cells was further confirmed by in vivo experiments. These results indicate that VASH1 acts as a cancer-inhibiting factor and potential therapeutic target in ovarian cancer.

Curaxin CBL0137 was designed to regulate p53 and nuclear factor-kappa B simultaneously and exhibits antitumor activity by inhibiting tumor cell proliferation and inducing apoptosis in multiple cancers. However, whether CBL0137 can induce pyroptosis has not yet been reported. This study demonstrated that CBL0137 induces caspase-3/gasdermin E (GSDME)-dependent pyroptosis via the reactive oxygen species (ROS)/BAX pathway. In ovarian cancer cells, CBL0137 inactivated the chromatin remodeling complex which could facilitate chromatin transcription, leading to the decreased transcription of antioxidant genes and oxidation and causing increased ROS levels. BAX was recruited on the mitochondrial membrane by mitochondrial ROS and induced the release of cytochrome c to cleave caspase-3. This led to the cleavage of the N-terminal of GSDME to form pores on the cell membrane and induced pyroptosis. Results of in vivo experiments revealed that CBL0137 also had anti-tumor effects on ovarian cancer cells in vivo. Our study outcomes reveal the mechanisms and targets of CBL0137 inducing pyroptosis in ovarian cancer cells and indicate that CBL0137 is a promising therapeutic agent for ovarian cancer.

BET proteins, which influence gene expression and contribute to the development of cancer, are epigenetic interpreters. Thus, BET inhibitors represent a novel form of epigenetic anticancer treatment. Although preliminary clinical trials have shown the anticancer potential of BET inhibitors, it appears that these drugs have limited effectiveness when used alone. Therefore, given the limited monotherapeutic activity of BET inhibitors, their use in combination with other drugs warrants attention, including the meaningful variations in pharmacodynamic activity among chosen drug combinations. In this paper, we review the function of BET proteins, the preclinical justification for BET protein targeting in cancer, recent advances in small-molecule BET inhibitors, and preliminary clinical trial findings. We elucidate BET inhibitor resistance mechanisms, shed light on the associated adverse events, investigate the potential of combining these inhibitors with diverse therapeutic agents, present a comprehensive compilation of synergistic treatments involving BET inhibitors, and provide an outlook on their future prospects as potent antitumor agents. We conclude by suggesting that combining BET inhibitors with other anticancer drugs and innovative next-generation agents holds great potential for advancing the effective targeting of BET proteins as a promising anticancer strategy. © 2023. The Author(s).

卵巢癌是全球女性生殖系统三大恶性肿瘤之一,严重威胁着女性的生命健康。近年来,研究者不断改进卵巢癌的治疗手段,但是卵巢癌的5年生存率依然并不乐观。随着精准医疗的推行,类器官模型的临床前研究逐渐进入科研工作者的视野。本文旨在

人纤维蛋白家族是一类广泛在各组织中表达的细胞外基质(ECM)蛋白,并在ECM的形成及稳定中发挥重要作用。越来越多的研究发现,Fibulin蛋白家族在不同的肿瘤组织中可分别起到抑癌或促癌的作用,从而影响肿瘤的增殖、侵袭、转移,并与肿瘤的

近年来,研究证明连接蛋白形成的间隙连接(Gap junction,GJ)在介导肿瘤细胞间通讯起到不可忽视的作用。而异常的连接蛋白26(Connexin 26,Cx26)表达也被证实与肿瘤的发生进展和不良预后相关,因此对Cx26进行生物标记物分析以及深入研究如

肿瘤细胞及其微环境中的细胞间通讯对肿瘤的发生发展至关重要。细胞间通讯可以通过多种机制发生,但是肿瘤组织中远隔细胞间的具体信息交流方式仍不清楚。隧道纳米管是一种可以将细胞直接连接起来的细长薄膜管道,作为新发现的细胞间通讯

Background Cervical cancer (CC) is the leading cause of cancer-related death in women. A limited number of studies have investigated whether immune-prognostic features can be used to predict the prognosis of CC. This study aimed to develop an improved prognostic risk scoring model (PRSM) for CC based on immune-related genes (IRGs) to predict survival and determine the key prognostic IRGs. Methods We downloaded the gene expression profiles and clinical data of CC patients from the TCGA and GEO databases. The ESTIMATE algorithm was used to calculate the score for both immune and stromal cells. Differentially expressed genes (DEGs) in different subpopulations were analyzed by "Limma". A weighted gene co-expression network analysis (WGCNA) was used to establish a DEG co-expression module related to the immune score. Immune-related gene pairs (IRGPs) were constructed, and univariate- and Lasso-Cox regression analyses were used to analyze prognosis and establish a PRSM. A log-rank test was used to verify the accuracy and consistency of the scoring model. Identification of the predicted key IRG was ensured by the application of functional enrichment, DisNor, protein-protein interactions (PPIs) and heatmap. Finally, we extracted the key prognostic immune-related genes from the gene expression data, validated the key genes by immunohistochemistry and analyzed the correlation between their expression and drug sensitivity. Results A new PRSM was developed based on 22 IRGPs. The prognosis of the low-risk group in the model group (P < 0.001) and validation group (P = 0.039) was significantly better than that in the high-risk group. Furthermore, M1 and M2 macrophages were highly expressed in the low-risk group. Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) and the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway were significantly enriched in the low-risk group. Three representative genes (CD80, CD28, and LCP2) were markers of CC prognosis. CD80 and CD28 may more prominent represent important indicators to improve patient prognosis. These key genes was positively correlated with drug sensitivity. Finally, we found that differences in the sensitivity to JNK inhibitors could be distinguished based on the use and risk grouping of this PRSM. Conclusions The prognostic model based on the IRGs and key genes have potential clinical significance for predicting the prognosis of CC patients, providing a foundation for clinical prognosis judgment and individualized treatment.