To explore the role of Methyltransferase-like 1 (METTL1) in the prognosis, diagnosis, and immune infiltration of Breast invasive carcinoma (BRCA), transcriptome data of BRCA from The Cancer Genome Atlas (TCGA) database were analyzed. Then, the METTL1 expression in normal and cancer tissues was compared using the DESeq2 package. Next, the diagnostic and prognostic value of METTL1 was evaluated using receiver operating characteristic curves and survival analysis, respectively. Co-expressed genes and differentially expressed genes related to METTL1 were identified using Pearson correlation and Wilcoxon tests, with overlapping genes subjected to protein-protein interaction network construction to identify hub genes via degree algorithm. After that, immune infiltration analyses were performed using CIBERSORT and xCELL algorithms. METTL1 expression was significantly higher in BRCA tissues compared to normal tissues, with significant diagnostic value. Furthermore, BRCA patients with low METTL1 expression showed better 5-year overall survival and disease specific survival than those with high METTL1 expression. A total of 1829 differentially expressed genes and 236 co-expressed genes were identified, with five hub genes selected. These genes, along with METTL1, were positively associated with immunosuppressive cell types, such as regulatory T cells and follicular helper T cells, suggesting their role in shaping an immunosuppressive tumor microenvironment.

Microbial dysbiosis has an increasingly appreciated impact on carcinogenesis, and the cervicovaginal microbiome plays a critical role in microenvironmental inflammation. Here, we investigated the involvement of the female genital tract Peptostreptococcus species in gynecological cancer via indoleacrylic acid (IAA). IAA production from Peptostreptococcus species and the effect of bacterial culture on tumor growth in vivo were examined. The impact of IAA on cytokine production and indoleamine-2,3-dioxygenase 1 (IDO1) expression in an endometrial cancer (EC) cell line, as well as their effect on Treg and Teff cells, and M1 and M2 macrophage populations were examined in EC patients and tumor-grafted mice. Clinically, Peptostreptococcus species abundance, IAA, and IDO1 expression were verified in EC patients. The results showed that IAA production was induced in the uteri of BALB/c nude mice by Peptostreptococcus species transplantation, and the intratumoral injection of a conditioned medium from Peptostreptococcus cultures into tumor-grafted mice promoted tumor growth. IL-10 expression was upregulated by IAA; IFN-γ expression was increased by IL-10. IFN-γ induced IDO1 expression in the EC cell line. The co-culture of IDO1-expressing EC cells with peripheral blood mononuclear cells upregulated the Treg proportion and decreased the M1/M2 ratio. Clinically, P. anaerobius was more abundant amongst the uterine microbiota of EC patients than the control. The IAA, IDO1, and kynurenine/tryptophan ratios were all higher in EC tissue, and the M1/M2 ratio was lower. Our study sheds light on the link between IDO1 induction and uterine Peptostreptococcus dysbiosis and provides a potential rationale for the role of Peptostreptococcus species in immune tolerance induction in type I endometrial cancer.

This study evaluated the inhibitory effects of calceolarioside B, extracted from the traditional Chinese herb Mutong (Akebia quinata Thumb), on the SARS-CoV-2 Omicron BA.2 variant. Molecular docking and molecular dynamics simulations predicted the binding sites and interactions between calceolarioside B and the Omicron BA.2 spike (S) protein. Biolayer interferometry (BLI) and immunofluorescence assays validated its high-affinity binding. Pseudovirus entry assays assessed the inhibitory effects of calceolarioside B on viral entry into host cells, while enzyme-linked immunosorbent assay (ELISA) measured inflammatory cytokine levels. Flow cytometry was used to analyze its effects on macrophage phenotype switching. Results demonstrated that calceolarioside B could bind to the Omicron BA.2 S protein with high affinity, and significantly inhibited viral entry into host cells by interfering with the binding of angiotensin-converting enzyme 2 (ACE2) receptor and S protein. Additionally, calceolarioside B reduced IL(interleukin)-6 expression levels and promoted the switch of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. These findings suggest that calceolarioside B possesses antiviral and immunomodulatory effects, making it a potential dual-function inhibitor for the treatment of COVID-19.

BACKGROUNDThe role of genes associated with the cuproptosis cell signaling pathway in prognosis and immunotherapy in ovarian cancer (OC) has been extensively investigated. In this study, we aimed to explore these mechanisms and establish a prognostic model for patients with OC using bioinformatics techniques.METHODSWe obtained the single cell sequencing data of ovarian cancer from the Gene Expression Omnibus (GEO) database and preprocessed the data. We analyzed a variety of factors including cuproptosis cell signal score, transcription factors, tumorigenesis and progression signals, gene set variation analysis (GSVA) and intercellular communication. Differential gene analysis was performed between groups with high and low cuproptosis cell signal scores, as well as Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Using bulk RNA sequencing data from The Cancer Genome Atlas, we used the least absolute shrinkage and selection operator (LASSO)-Cox algorithm to develop cuproptosis cell signaling pathword-related gene signatures and validated them with GEO ovarian cancer datasets. In addition, we analyzed the inherent rules of the genes involved in building the model using a variety of bioinformatics methods, including immune-related analyses and single nucleotide polymorphisms. Molecular docking is used to screen potential therapeutic drugs. To confirm the analysis results, we performed various wet experiments such as western blot, cell counting kit 8 (CCK8) and clonogenesis tests to verify the role of the Von Willebrand Factor (VWF) gene in two ovarian cancer cell lines.RESULTSBased on single-cell data analysis, we found that endothelial cells and fibroblasts showed active substance synthesis and signaling pathway activation in OC, which further promoted immune cell suppression, cancer cell proliferation and metastasis. Ovarian cancer has a high tendency to metastasize, and cancer cells cooperate with other cells to promote disease progression. We developed a signature consisting of eight cuproptosis-related genes (CRGs) (MAGEF1, DNPH1, RARRES1, NBL1, IFI27, VWF, OLFML3 and IGFBP4) that predicted overall survival in patients with ovarian cancer. The validity of this model is verified in an external GEO validation set. We observed active infiltrating states of immune cells in both the high- and low-risk groups, although the specific cells, genes and pathways of activation differed. Gene mutation analysis revealed that TP53 is the most frequently mutated gene in ovarian cancer. We also predict small molecule drugs associated with CRGs and identify several potential candidates. VWF was identified as an oncogene in ovarian cancer, and the protein was expressed at significantly higher levels in tumor samples than in normal samples. The high-score model of the cuproptosis cell signaling pathway was associated with the sensitivity of OC patients to immunotherapy.CONCLUSIONSOur study provides greater insight into the mechanisms of action of genes associated with the cuproptosis cell signaling pathway in ovarian cancer, highlighting potential targets for future therapeutic interventions.

Elucidating the mechanism for the high metastasis capacity of Endometrial cancer (EC) is crucial to improve treatment outcomes of EC. We have recently reported that nicotinamide N-methyltransferase (NNMT) is overexpressed in EC, especially in EC, and predicts poor survival of chemotherapy patients. Here, we aimed to determine the function and mechanism of NNMT on metastasis of EC. Additionally, analysis of public datasets indicated that NNMT is involved in cholesterol metabolism. In vitro, NNMT overexpression promoted migration and invasion of EC by reducing cholesterol levels in the cytoplasm and cell membrane. Mechanistically, NNMT activated ABCA1 expression, leading to cholesterol efflux and membrane fluidity enhancement, thereby promoting EC's epithelial-mesenchymal transition (EMT). In vivo, the metastasis capacity of EC was weakened by targeting NNMT. Our findings suggest a new molecular mechanism involving NNMT in metastasis, poor survival of EC mediated by PP2A and affecting cholesterol metabolism.

Background Numerous studies indicate that long noncoding RNA (lncRNA) is aberrantly expressed in ovarian cancer (OC). Our research investigated the regulatory role of lncRNA KTN1 antisense RNA1 (KTN1-AS1) in the progression of OC through the miR-505-3p/ZNF326 axis. Methods Expression of KTN1-AS1, microRNA-505-3p (miR-505-3p), and zinc-finger protein-326 (ZNF326) in OC was evaluated by using RT-qPCR analysis. The biological function of KTN1-AS1 was inspected using the loss-of-function assay. Luciferase reporter assay and RIP assay were performed to determine the competitive endogenous RNA (ceRNA) network of KTN1-AS1/miR-505-3p/ZNF326. Results The data showed that KTN1-AS1 and ZNF326 had a high expression in OC than in the normal tissue, and miR-505-3p exhibited a low expression in OC than in the normal tissue. The knockdown of KTN1-AS1 caused an inhibition in OC cell proliferation, migration, and invasion, and promoted cell apoptosis. In terms of mechanical exploration, KTN1-AS1 was transcriptionally activated by histone H3 on lysine 27 acetylation (H3K27ac) at the promoter region, and KTN1-AS1 increased ZNF326 expression by competitively adsorbing miR-505-3p. Conclusions This study indicated that H3K27ac-induced lncRNA KTN1-AS1 expression, and facilitated proliferation, migration, and invasion of OC cells by the KTN1-AS1/miR-505-3p/ZNF326 axis.

The article presents a concentric circle compound reconfigurable (frequency, polarization, and pattern) microstrip antenna for lower-S band (2.0 GHz-3.0 GHz) applications. Varying the capacitance of four varactor diodes from 4.15pF (0 V) to 0.94pF (6 V), the resonant frequency of the antenna can be tuned from 2.10 GHz to 2.90 GHz (34.52% tunable bandwidth). These diodes are incorporated to bridge the gap between the circle and ring of concentric geometry. The arc slots and C-shape wings are used for polarization and pattern reconfiguration, respectively. The arc slots are etched from the edge of circle geometry and loaded with RF PIN diodes to provide the different polarization states: linear polarization, left-hand circular polarization (LHCP), and right-hand circular polarization (RHCP). Simultaneously, the pattern reconfigurability can be attained with C-shape wings, placed around the concentric circle geometry; hence, patterns are tilt at 0° and ± 50°. The pattern reconfigurability also controlled through the RF PIN diodes. The designed antenna is experimentally verified and shows the maximum gain of 4.31 dBic and 4.04 dBi in polarization and pattern reconfigurable mode, respectively. Besides, it provides an excellent axial ratio (<3 dB) and stable radiation patterns. Therefore, the proposed compound reconfigurable antenna can be served for a future communication system and improves the signal quality without any destruction.

Purpose The effects of cigarette smoking on male semen quality are controversial, and the molecular mechanisms underlying how cigarette smoking affects semen quality are not clear yet. Methods In this study, semen samples from 70 heavy smokers and 75 non-smokers receiving infertility treatment were included. Basic semen parameters in non-smokers and heavy smokers were evaluated. Levels of glutathione (GSH), lipid reactive oxygen species (ROS), iron and GSH-dependent peroxidase 4 (GPX4) protein level) were observed in human seminal plasma and in GC-2 Spd cells exposed to cigarette smoke condensate (CSC). Results Heavy smokers had significantly higher abnormalities (sperm viability and sperm progressive motility) than non-smoking counterparts. Comparing non-smokers group, GSH level was reduced in the group of heavy smokers (P<0.05). However, the level of lipid ROS and iron were significantly increased (P<0.05). Besides, GSH level was reduced following treatment with CSC for 24 h, while lipid ROS and iron levels were increased (P<0.05). However, the levels were reduced after being co-cultured with Ferrostatin-1 (Fer-1) (P<0.05). The level of GPX4 protein was reduced after being treated with CSC in 24 h, and increased after being co-cultured with Fer-1(P<0.05). Conclusion Cigarette smoking is associated with high level of ferroptosis in seminal plasma and affect semen quality.

Abstract Purpose The effects of cigarette smoking on male semen quality are controversial, and the molecular mechanisms underlying how cigarette smoking affects semen quality are not clear yet. Methods In this study, semen samples from 70 heavy smokers and 75 non-smokers receiving infertility treatment were included. Basic semen parameters in non-smokers and heavy smokers were evaluated. Levels of ferroptosis glutathione (GSH), lipid reactive oxygen species (ROS), iron and GSH-dependent peroxidase 4 (GPX4) protein level) were observed in human semen and in GC-2 Spd cells exposed to cigarette smoke condensate (CSC). Results Heavy smokers had significantly higher abnormalities (sperm viability and sperm progressive motility) than non-smoking counterparts. Comparing non-smokers group, GSH level was reduced in the group of heavy smokers (P<0.05). However, the level of lipid ROS and iron were significantly increased (P<0.05). Besides, GSH level was reduced following treatment with CSC for 24 h, while lipid ROS and iron levels were increased (P<0.05). However, the levels were reduced after being co-cultured with Ferrostatin-1 (Fer-1) (P<0.05). The level of GPX4 protein was reduced after being treated with CSC in 24 h, and increased after being co-cultured with Fer-1(P<0.05). Conclusion Cigarette smoking is associated with abnormalities of ferroptosis in human sperm.

Microbial dysbiosis has an increasingly appreciated impact on carcinogenesis and cervicovaginal microbiome plays a critical role in microenvironmental inflammation. Here we investigated the involvement of the female genital tract microbiome in a gynaecological cancer. We transferred Peptostreptococcus species into the uteri of BALB/c nude mice and observed indoleacrylic acid (IAA) production. Intratumoral injection of conditioned medium from bacterial cultures into tumour-xenografted mice for 2 months promoted tumour growth. IAA upregulated IL-10 expression by M2 macrophages, which increased IFN-γ expression by CD8+ T cells. IFN-γ induced indoleamine-2,3-dioxygenase 1 (IDO1) expression in endometrial cancer (EC) cell line. Co-culture of IDO1-expressing EC cells with peripheral blood mononuclear cells upregulated the proportion of regulatory T cells and decreased the M1/M2 ratio. Importantly, P. anaerobius was more abundant amongst the uterine microbiota of clinical EC patient samples than control samples. IAA, IDO1, and the kynurenine/tryptophan ratio were all higher in EC tissue than in healthy tissue, and the M1/M2 ratio was lower. Thus, we conclude that the overabundance of uterine commensal Peptostreptococcus species in EC induces IDO1 expression by producing IAA. Our study sheds light on the link between IDO1 induction and uterine Peptostreptococcus dysbiosis.

Damage-associated molecular pattern molecules (DAMPs) are endogenous danger signals that alert the innate immune system and shape the inflammation response to cell death. However, the release and activity of DAMPs in ferroptosis, a recently identified form of regulated necrosis characterized by iron overload and lipid peroxidation, still remain poorly understood. Here, we demonstrate that HMGB1 is a DAMP released by ferroptotic cells in an autophagy-dependent manner. Both type I and II ferroptosis activators, including erastin, sorafenib, RSL3, and FIN56, induce HMGB1 release in cancer and noncancer cells. In contrast, genetic ablation (using ATG5−/− or ATG7−/− cells) or pharmacologic inhibition (the administration of bafilomycin A1 or chloroquine) of autophagy was found to block ferroptosis activator-induced HMGB1 release. Mechanically, autophagy-mediated HDAC inhibition promotes HMGB1 acetylation, resulting in HMGB1 release in ferroptosis. Moreover, AGER, but not TLR4, is required for HMGB1-mediated inflammation in macrophages in response to ferroptotic cells. These studies suggest that HMGB1 inhibition might have some potential therapeutic effects in ferroptosis-associated human disease.

To explore the antitumor effect of hypoxia-inducible factor-1α short hairpin RNA (HIF-1α shRNA) delivered by ultrasound targeted microbubble destruction (UTMD) and transcatheter arterial embolization (TAE) on rats with hepatic cancer. After the models of transplantation hepatoma were established, Wistar rats were randomly divided into 4 groups: Control group, UTMD group, TAE group, and UTMD+TAE group. Contrast-enhanced ultrasound (CEUS) was used to monitor tumor size on day 14 after four different treatments. Western blotting and immunohistochemistry were applied to measure the protein level of HIF-1α and VEGF in the hepatic cancer tissue. In comparison with UTMD+TAE group (21.25±10.68 days), the mean survival time was noticeably shorter in the Control group and TAE group (13.02±4.30 days and 15.03±7.32 days) (p<0.05, respectively). There was no statistical difference between UTMD+TAE group and UTMD group of the mean survival time (p>0.05). In addition, our results proved that the tumor sizes in UTMD+TAE group were obviously smaller than those in other groups (p<0.05, respectively). By CEUS, we clearly found that the tumor size was the smallest on day 14 in the UTMD+TAE group. The western blotting and immunohistochemistry results proved that the protein levels of HIF-1α and VEGF in UTMD+TAE group were obviously lower than those in TAE group and Control group on days 7 and 14 (p<0.05, respectively). However, there was no statistical difference between UTMD+TAE group and UTMD group (p>0.05). In this study we tried to explore the antitumor effect through a combination of UTMD-mediated HIF-1α shRNA transfection and TAE on rats with hepatic cancer. Our results showed that UTMD-mediated HIF-1α shRNA transfection and TAE can obviously silence HIF-1α and VEGF expression, thereby successfully inhibiting the growth of the tumor.

Pancreatic cancer is an aggressive malignancy with changes in the tumor microenvironment. Here, we demonstrate that PINK1 and PARK2 suppressed pancreatic tumorigenesis through control of mitochondrial iron-dependent immunometabolism. Using mouse models of spontaneous pancreatic cancer, we show that depletion of Pink1 and Park2 accelerates mutant Kras-driven pancreatic tumorigenesis. PINK1-PARK2 pathway-mediated degradation of SLC25A37 and SLC25A28 increases mitochondrial iron accumulation, which leads to the HIF1A-dependent Warburg effect and AIM2-dependent inflammasome activation in tumor cells. AIM2-mediated HMGB1 release further induces expression of CD274/PD-L1. Consequently, pharmacological administration of mitochondrial iron chelator, anti-HMGB1 antibody, or genetic depletion of Hif1a or Aim2 in pink1-/- and park2-/- mice confers protection against pancreatic tumorigenesis. Low PARK2 expression and high SLC25A37 and AIM2 expression are associated with poor prognosis in patients with pancreatic cancer. These findings suggest that disrupted mitochondrial iron homeostasis may contribute to cancer development and hence constitute a target for therapeutic intervention.

Ferroptosis is a form of regulated cell death triggered by lipid peroxidation after inhibition of the cystine/glutamate antiporter system Xc-. However, key regulators of system Xc- activity in ferroptosis remain undefined. Here, we show that BECN1 plays a hitherto unsuspected role in promoting ferroptosis through directly blocking system Xc- activity via binding to its core component, SLC7A11 (solute carrier family 7 member 11). Knockdown of BECN1 by shRNA inhibits ferroptosis induced by system Xc- inhibitors (e.g., erastin, sulfasalazine, and sorafenib), but not other ferroptosis inducers including RSL3, FIN56, and buthionine sulfoximine. Mechanistically, AMP-activated protein kinase (AMPK)-mediated phosphorylation of BECN1 at Ser90/93/96 is required for BECN1-SLC7A11 complex formation and lipid peroxidation. Inhibition of PRKAA/AMPKα by siRNA or compound C diminishes erastin-induced BECN1 phosphorylation at S93/96, BECN1-SLC7A11 complex formation, and subsequent ferroptosis. Accordingly, a BECN1 phosphorylation-defective mutant (S90,93,96A) reverses BECN1-induced lipid peroxidation and ferroptosis. Importantly, genetic and pharmacological activation of the BECN1 pathway by overexpression of the protein in tumor cells or by administration of the BECN1 activator peptide Tat-beclin 1, respectively, increases ferroptotic cancer cell death (but not apoptosis and necroptosis) in vitro and in vivo in subcutaneous and orthotopic tumor mouse models. Collectively, our work reveals that BECN1 plays a novel role in lipid peroxidation that could be exploited to improve anticancer therapy by the induction of ferroptosis.

Sepsis is a life-threatening condition caused by pathogen infection and associated with pyroptosis. Pyroptosis occurs upon activation of proinflammatory caspases and their subsequent cleavage of gasdermin D (GSDMD), resulting in GSDMD N-terminal fragments that form membrane pores to induce cell lysis. Here, we show that antioxidant defense enzyme glutathione peroxidase 4 (GPX4) and its ability to decrease lipid peroxidation, negatively regulate macrophage pyroptosis, and septic lethality in mice. Conditional Gpx4 knockout in myeloid lineage cells increases lipid peroxidation-dependent caspase-11 activation and GSDMD cleavage. The resultant N-terminal GSDMD fragments then trigger macrophage pyroptotic cell death in a phospholipase C gamma 1 (PLCG1)-dependent fashion. Administration of the antioxidant vitamin E that reduces lipid peroxidation, chemical inhibition of PLCG1, or genetic Caspase-11 deletion or Gsdmd inactivation prevents polymicrobial sepsis in Gpx4-/- mice. Collectively, this study suggests that lipid peroxidation drives GSDMD-mediated pyroptosis and hence constitutes a potential therapeutic target for lethal infection.

BACKGROUND:Ovarian carcinoma is one of the most aggressive gynecological malignant neoplasms and makes up 25-30% of all cancer cases of the female genital tract. Currently, resistance to traditional chemotherapy is a great challenge for patients with Epithelial ovarian cancer (EOC). Therefore, identifying novel agents for EOC treatment is essential and urgent.METHOD:MTS assay was used to analyze the cell viability and proliferation of cancer cells. Flow cytometry was employed to analyze cell cycle distribution and cell apoptosis. Protein signaling pathways were detected by western blot and immunohistochemical staining. Nude mouse experiment was performed to test the in vivo effect of platinum pyrithione (PtPT).RESULTS:PtPT is a chemically well-characterized synthetic complex of platinum that potently inhibits proteasome-associated deubiquitinases USP14 and UCHL5 activity and shows selective cytotoxicity to multiple cancer cells without damaging DNA. We found that PtPT significantly accumulated ubquitinated-proteins and suppressed the proliferation of multiple EOC cells. Additionally, PtPT induced G2 phase arrest and apoptosis in both A2780 and SKOV3 cells. More importantly, animal experiments showed that PtPT dramatically suppressed the growth of EOC xenografts without obvious side effects.CONCLUSION:These results suggest that through proteasome inhibition, PtPT significantly suppressed the proliferation of EOC in vitro and in vivo and could be developed as a novel agent for EOC treatment in the future.

Objectives The aims of this study were to investigate the functions of GAS5 as a tumor suppressor in cervical cancer and explore the mechanism. Methods The expression of GAS5 and microRNA 21 (miR-21) was detected in primary cervical cancer tissue specimens, as well as in cervical cancer cell lines. We identified the interaction of GAS5 and miR-21 by quantitative polymerase chain reaction, Western blot, and dual-luciferase reporter assay. We also studied the functions of GAS5 in proliferation, apoptosis, migration, and invasion in cervical cancer cells in vitro and vivo. Finally, the impact of GAS5 on cisplatin resistance and its mechanism in cervical cancer cells was also identified. Results The expression of GAS5 and miR-21 was detected in primary cervical cancer tissue specimens, as well as in cervical cancer cell lines. GAS5, which is a tumor suppressor playing roles in inhibiting the malignancy of cervical cancer cells, including proliferation in vivo and vitro, migration, and invasion, has a low expression in cervical cancer tissue and cervical cancer cell lines, whereas miR-21 expression is high. GAS5 significantly decreased the expression of miR-21, and there is a reciprocal repression of gene expression between GAS5 and miR-21. Besides, most importantly, we found that high expression of GAS5 and low expression of miR-21 can enhance the sensitivity of SiHa/cDDP cancer cells to cisplatin. A further experiment for identifying the mechanism of cisplatin resistance by GAS5 showed that GAS5 can not only regulate phosphatase and tensin homolog through miR-21 but also influence the phosphorylation of Akt. Conclusions Our results indicate that GAS5 is a direct target of miR-21 and can predict the clinical staging of cervical cancer. Most importantly, GAS5 can also influence cisplatin resistance in cervical cancer via regulating the phosphorylation of Akt. All of these suggest that GAS5 may be a novel therapeutic target for treating cervical cancer.

BackgroundMetastasis associated in lung adenocarcinoma transcript-1 (MALAT-1) is overexpressed during cancer progression and promotes cell migration and invasion in many solid tumors. However, its role in ovarian cancer remains poorly understood.MethodsExpressions of MALAT-1 were detected in 37 normal ovarian tissues and 45 ovarian cancer tissues by reverse transcription polymerase chain reaction (RT-PCR). Cell proliferation was observed by CCK-8 assay; Flow cytometry was used to measure cell cycle and apoptosis; Cell migration was detected by transwell migration and invasion assay. In order to evaluate the function of MALAT-1, shRNA combined with DNA microarray and Functional enrichment analysis were performed to determine the transcriptional effects of MALAT-1 silencing in OVCAR3 cells. RNA and protein expression were measured by qRT-PCR and Western blotting, respectively.ResultsWe found that upregulation of MALAT-1 mRNA in ovarian cancer tissues and enhanced MALAT-1 expression was associated with FIGO stage. Knockdown of MALAT-1 expression in OVCAR3 cells inhibited cell proliferation, migration, and invasion, leading to G0/G1 cell cycle arrest and apoptosis. Overexpressed MALAT-1 expression in SKOV3 cells promoted cell proliferation, migration and invasion. Downregulation of MALAT-1 resulted in significant change of gene expression (at least 2-fold) in 449 genes, which regulate proliferation, cell cycle, and adhesion. As a consequence of MALAT-1 knockdown, MMP13 protein expression decreased, while the expression of MMP19 and ADAMTS1 was increased.ConclusionsThe present study found that MALAT-1 is highly expressed in ovarian tumors. MALAT-1 promotes the growth and migration of ovarian cancer cells, suggesting that MALAT-1 may be an important contributor to ovarian cancer development.

目的:通过检测细胞分裂周期蛋白6 (cell division cycle protein 6,CDC6)在不同级别宫颈病变中的表达,探讨其在宫颈病变中的意义.方法:收集宫颈组织石蜡标本122例,采用免疫组化S-P法检测宫颈组织中CDC6蛋白的表达.结果:CDC6阳性着色位于细胞核及胞浆,其表达阳性率分别为:宫颈正常组5.00％(1/20)、CIN Ⅰ组35.00％(7/20)、CINⅡ～Ⅲ组71.43％(30/42)、宫颈癌组87.50％(35/40),各组间差异有统计学意义(x2=36.57,P＜0.001).在122例宫颈石蜡标本中,HPV感染阳性者83例,其中CDC6蛋白表达阳性率为73.49.45％(61/83);HPV感染阴性者39例,其中CDC6蛋白表达的阳性率为30.77％(12/39),两者比较差异有统计学意义(x2=20.15,P＜0.005);CDC6蛋白的表达与HPV感染呈正相关(r=0.769).结论:CDC6的表达与宫颈病变的发生发展密切相关,其与HPV感染在宫颈病变中可能存在协同作用.