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Objectives: Long non-coding RNAs (lncRNAs) are playing important roles in cancer progression and metastasis. Recent studies have demonstrated that the lncRNA, nuclear paraspeckle assembly transcript 1 (NEAT1), was aberrantly up-regulated in various types of cancers and was reported to be associated with unfavorable prognosis in cancer patients. This study examined the relationship between NEAT1 and relevant clinical outcomes., Results: A total of 1354 patients from 11 eligible studies were included in the meta-analysis. The results showed that high expression level of NEAT1 was significantly associated with shorter overall survival in cancer patients (hazard ratio (HR) = 1.53, 95% confidence interval (CI) = 1.36-1.71); in the subgroup analysis, the positive association was also found in patients with hepato-gastroenterol cancers (HR = 1.79, 95% CI = 1.48-2.16), non-small cell lung cancer (HR = 1.35, 95% CI = 1.04-1.76), ovarian cancer (HR = 1.41, 95% CI = 1.11-1.79) and other types of cancers (HR = 1.42, 95% CI = 1.11-1.81). The clinicopathological parameters analysis further showed that increased expression level of NEAT1 was positively correlated with larger tumor size (odds ratio (OR) = 1.74, 95% CI = 1.26-2.41), lymph node metastasis (OR = 2.29, 95% CI = 1.71-3.06), advanced TNM stage (OR = 3.60, 95% CI = 2.27-5.72), poor tumor differentiation (OR = 2.16, 95% CI = 1.58-2.93), distant metastasis (OR = 3.51, 95% CI = 1.75-7.01), and invasion depth (OR = 1.94, 95% CI = 1.36-2.75)., Materials and Methods: A comprehensive search was performed in Pubmed, Embase, Web of Science and CNKI databases, and eligible studies were included based on defined exclusion and inclusion criteria to perform meta-analysis., Conclusions: The meta-analysis results from present study suggested that increased expression level of NEAT1 was associated with unfavorable prognosis and may serve as a predictive factor for clinicopathological features in various cancers.

Background: Endometrial carcinoma ranks as the second most widespread malignancy affecting the reproductive system in females. Effective prognostic biomarkers are required to further improve survival rates for patients. Single-minded homolog 2 (SIM2) is known to participate in neurogenesis as a transcription factor. However, the potential role of SIM2 in endometrial carcinoma remains elusive.Methods: Multiple public databases, including TIMER2.0, GEIPA2, UALCAN, LinkedOmics, BioGRID, DAVID and cBioPortal, were used to investigate SIM2 mRNA expression, SIM2-associated genes, PPI network, functional enrichment analysis, SIM2 gene alterations and methylation. The association between SIM2 expression and immune cell infiltrates was explored using GSVA. The effects of gene alterations and methylation on patient survival and CD8+T infiltration were examined using GSCA. Moreover, the prognostic potential of SIM2 was evaluated using COX regression, ROC curves and a nomogram model. Finally, the differential expression and function of SIM2 in UCEC were explored using qPCR, WB, CCK8 and Transwell assays.Results: Our findings revealed the heightened expression of SIM2 in endometrial carcinoma, and that its DNA methylation and CNV alterations were correlated with immune infiltration and patients' prognosis. Additionally, functional enrichment revealed the involvement of SIM2 in transcription regulation and signal transduction. Moreover, we performed cell-based experiments to corroborate the oncogenic function of SIM2 in facilitating cell proliferation, migration and invasion.Conclusion: Collectively, these results suggest that SIM2 holds promise as both a potential prognostic indicator and a viable treatment target for endometrial carcinoma. [ABSTRACT FROM AUTHOR]

Background. NKG2A (KLRC1) belongs to the NKG2 family, which has been shown to affect the activity of natural killer (NK) cells and CD8T cells. However, a comprehensive biological analysis and exploration of NKG2A in different cancers is lacking and this needs to be further investigated. Methods. A comprehensive pan-cancer analysis of NKG2A was performed based on multiple databases. The Cancer Genome Atlas (TCGA) and Genotype–Tissue Expression (GTEx) databases were used to analyze the expression profile of NKG2A in pan-cancer. The relevance of NKG2A to the prognosis of different cancers was assessed using Kaplan–Meier survival analysis. In addition, we explored the correlation between NKG2A expression and gene mutations, pathological staging, tumor-infiltrating immune cells (TIICs), DNA methyltransferase (DNMT) genes, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and immune checkpoints (ICPs). Finally, the expression levels of NKG2A in several cancer cell lines were verified by qRT-PCR. Results. Pan-cancer comprehensive analysis showed that NKG2A expression levels were significantly different between multiple cancers and corresponding normal tissues. The differential expression of NKG2A was related to the prognosis and pathological staging of patients with multiple cancers, and was closely related to the excessive infiltration of immune cells and the regulation of ICP genes in the tumor microenvironment (TME). In addition, TMB, MSI, MMR, and DNMT genes in many cancer types are also affected by NKG2A expression. Gene set enrichment analysis (GSEA) showed that NKG2A was associated with multiple immune-related functions and pathways in malignant tumors. qRT-PCR results showed that NKG2A was underexpressed in liver, gastric, and colon cancer cell lines compared to normal cells, which was consistent with bioinformatics analysis. Conclusion. The present study suggests that NKG2A may be a potential predictive biomarker for cancer immune response and prognosis. [ABSTRACT FROM AUTHOR]

The malignant phenotypes of cancer are defined not only by its intrinsic tumor cells but also by the tumor infiltrating immune cells (TIICs) recruited to the cancer microenvironment. Clear cell renal cell carcinoma (ccRCC) immune microenvironment plays an important role in the tumorigenesis. This research investigated the characteristics of immune cell invasion of renal cell carcinoma and provided clues for future clinical implementation. Retrospectively, ccRCC gene expression was analyzed with appropriate clinicopathological data from the Cancer Genome Atlas (TCGA) and GEO database up to December 2019. The CIBERSORT algorithm, meta-analysis, principal component analysis (PCA), Single-Sample Gene Set Enrichment Analysis (ssGSEA) and hierarchical agglomerative clustering were used to measure and evaluate the respective proportions of 22 cell types of immune infiltration using normalized gene expression data. We also focused on evaluating the association with TIICs subpopulations and clinical features and molecular subtypes. TIICs subpopulation, especially Macrophages subgroup, T follicular helper (Tfh) cells and CD8 T cells, all contribute to tumorigenesis. Unsupervised clustering analysis revealed that there existed two distinct TIICs subgroups with different survival patterns. TIICs are extensively involved in the pathogenesis and development of the ccRCC. Characterizing the composition of TIICs influences the metabolism of tumors, activity, level, stage, and survival of patients. Collectively, the TIIC analysis has the potential to assist in the assessment and selection of ccRCC prognosis and treatment. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) have been revealed to play vital roles in modulating gene expression and participate in several pathological responses including gastric cancer (GC). However, the larger numbers of the circRNAs in GC progression remain undetermined. In the present study, four GC related circRNAs expression profiles from the Gene Expression Omnibus (GEO) database were enrolled. We identified hsa_ circRNA_00067997 (circ_0067997) as an oncogene in GC. qRT-PCR was used to validate the expression of circ_0067997 in GC tissues and cell lines. The results revealed that circ_0067997 was upregulated in GC, and high circ_0067997 expression was associated with the poor overall survival rate of GC patients. Knockdown of circ_0067997 significantly reduced cell viability, inhibited colony formation, and attenuated invasive ability, whereas overexpression of circ_0067997 exhibited opposed effects. Circ_0067997 was identified to be a sponge for miR-515-5p directly. Moreover, XIAP was demonstrated to be targeted and regulated by miR-515-5p. In conclusion, circ_0067997 was identified to be an oncogene in GC by regulating miR-515-5p/XIAP axis. [ABSTRACT FROM AUTHOR]

Background: Chinese traditional herbal medicine Fuzhengkangai (FZKA) formulation combination with gefitinib can overcome drug resistance and improve the prognosis of lung adenocarcinoma patients. However, the pharmacological and molecular mechanisms underlying the active ingredients, potential targets, and overcome drug resistance of the drug are still unclear. Therefore, it is necessary to explore the molecular mechanism of FZKA. Methods: A systems pharmacology and bioinformatics-based approach was employed to investigate the molecular pathogenesis of EGFR-TKI resistance with clinically effective herb formula. The differential gene expressions between EGFR-TKI sensitive and resistance cell lines were calculated and used to find overlap from targets as core targets. The prognosis of core targets was validated from the cancer genome atlas (TCGA) database by Cox regression. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment is applied to analysis core targets for revealing mechanism in biology. Results: The results showed that 35 active compounds of FZKA can interact with eight core targets proteins (ADRB2, BCL2, CDKN1A, HTR2C, KCNMA1, PLA2G4A, PRKCA and LYZ). The risk score of them were associated with overall survival and relapse free time (HR = 6.604, 95% CI: 2.314–18.850; HR = 5.132, 95% CI: 1.531–17.220). The pathway enrichment suggested that they involved in EGFR-TKI resistance and non-small cell lung cancer pathways, which directly affect EGFR-TKI resistance. The molecular docking showed that licochalcone a and beta-sitosterol can closely bind two targets (BCL2 and PRKCA) that involved in EGFR-TKI resistance pathway. Conclusions: This study provided a workflow for understanding mechanism of CHM for against drug resistance. [ABSTRACT FROM AUTHOR]

Background & Aims Aberration of miR-129-2 has been linked to a variety of human tumours. However, whether miR-129-2 is involved in hepatocarcinogenesis remains unknown. Here, we investigate the involvement of miR-129-2 in HBV infection-related HCC. Methods A total of 75 paired tumour and their corresponding non-tumour liver tissues from HCC patients with serum HBs Ag positive were collected. The methylation of miR-129-2 gene was quantitatively analysed by a DNA methylation-sensitive endonuclease digestion followed by quantitative PCR. The expression of mature miR-129-2 (miR-129-3p) was detected by Taqman RT- PCR. SOX4 expression was detected using quantitative realtime RT- PCR, western blot and immunohistochemical staining. The function of miR-129-2 was investigated using cell proliferation and clonogenicity assays in vitro. Results Compared with the adjacent non-tumour tissues, tumour tissues exhibited significantly increased miR-129-2 hypermethylation both in frequency (37.33% vs. 8%, P < 0.0001) and in intensity (14.77% vs. 3.08%, P = 0.002). Accordantly, miR-129-3p expression in HCC tissues was significantly lower than that in non-tumour tissues ( P = 0.0461), in a manner reversely correlated with the level of miR-129-2 hypermethylation. Notably, SOX4 level in the HCC tissues was significantly higher than that in non-tumour tissues ( P = 0.0174) and normal liver tissues ( P = 0.0077), correlated reversely with miR-129-3p level ( P = 0.0105). Furthermore, overexpression of miR-129-2 in HepG2 reduced cell proliferation and clonogenicity, while co-expression with SOX4 could partially reverse its antitumor effects. In addition, SOX4 in HepG2 cell can enhance β-catenin/TCF activity by increasing β-catenin level. Conclusion The current data indicated that methylation-mediated repression of miR-129-2 may enhance oncogenic SOX4 expression and involve in HCC tumorigenesis. [ABSTRACT FROM AUTHOR]

Mancozeb (MZ), an antibacterial pesticide, has been linked to reproductive toxicity, neurotoxicity, and endocrine disruption. However, whether MZ has cardiactoxicity is unclear. In this study, the cardiotoxic effects of exposure to environment-related MZ concentrations ranging from 1.88 μM to 7.52 μM were evaluated at the larval stage of zebrafish. Transcriptome sequencing predicted the mechanism of MZ-induced cardiac developmental toxicity in zebrafish by enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). Consistent with morphological changes, the osm , pfkfb3, foxh1 , stc1, and nrarpb genes may effect normal development of zebrafish heart by activating NOTCH signaling pathways, resulting in pericardial edema, myocardial fibrosis, and congestion in the heart area. Moreover, differential gene expression analysis indicated that cyp-related genes (cyp1c2 and cyp3c3) were significantly upregulated after MZ treatment, which may be related to apoptosis of myocardial cells. These results were verified by real-time quantitative RT-qPCR and acridine orange staining. Our findings suggest that MZ-mediated cardiotoxic development of zebrafish larvae may be related to the activation of Notch and apoptosis-related signaling pathways. [Display omitted] • RNA sequencing predicts the mechanism of MZ-induced cardiotoxicity in zebrafish. • Transcriptomic analysis indicated the Notch signaling pathway may be related to the cardiotoxicity of zebrafish embryos. • Activating AhR signaling pathway may be related to zebrafish cardiomyocyte apoptosis and cardiac malformations. [ABSTRACT FROM AUTHOR]

Numerous studies have indicated that the aberrant expression of LINC00963 is extensively present in various human tumors, and that dysregulation of LINC00963 is implicated in the initiation and progression of human cancers. In this meta-analysis, data from diverse malignancies were analyzed to determine whether LINC00963 expression levels were associated with clinical prognosis and immune infiltration in pan-cancer. The eligible studies were identified from several electronic databases from the inception to July 2022 through systematic research. LINC00963 expression and survival were estimated using pooled odds ratios and hazard ratios with 95% CI. We used the Kaplan-Meier method and COX analysis for survival analysis. In addition, Spearman's correlation analysis was used to uncover any correlation between LINC00963 and microsatellites instability (MSI), tumor mutational burden (TMB), DNA methyltransferases (DNMTs), immune checkpoint biomarkers, and the related genes of mismatch repair (MMR). Our findings indicated that overexpression of LINC00963 was related to poor overall survival (OS) (HR =1.32, 95% CI, 1.09–1.59, P = 0.004). The TCGA database also found that abnormal expression of LINC00963 was linked to overall survival in various cancers. Moreover, there is an association between LINC00963 expression and MSI, TMB, and MMR in malignancies of various types. The results of this study indicate that LINC00963 may serve as a prognostic biomarker and a therapeutic target for cancer. By using it, cancer diagnoses can be improved, treatment targets discovered, and prognostic questions improved. [ABSTRACT FROM AUTHOR]