Genetics research最新文献

Background: Cysteine and Glycine Rich Protein 1 (CSRP1) belongs to the cysteine-rich protein family, which contains a unique double-zinc finger motif and is important for development and cellular differentiation. Abnormal expression of CSRP1 was reported within several malignancies such as prostate cancer and acute myeloid leukemia. Here, we explored function of CSRP1 within colon adenocarcinoma (COAD) for the first time.

Methods: The mRNA levels of CSRP1 in COADs were obtained from TCGA datasets. CSRP1 protein expressions in COADs were tested via immunohistochemistry staining. Patients' prognosis was evaluated using both univariate analysis and multivariate analysis. Two human COAD originated cancer cell lines, Caco-2, and HT-29, were used for cellular experiments including shRNA knockdown, proliferation assay, and migration assay. In vivo model was established using nude mice xenografts to further validate the role of CSRP1 in COAD progression.

Results: The mRNA levels of CSRP1 are elevated in COAD specimens from patients with more advanced tumor stages and higher Carcinoembryonic Antigen (CEA) levels. In addition, higher CSRP1 mRNA level indicates worse COAD prognosis. Consistently, higher CSRP1 protein expression is correlated with worse overall survival according to both univariate and multivariate analysis, indicating that CSRP1 is a new COAD prognostic factor. Furthermore, COAD cells transfected with CSRP1-shRNAs exhibit attenuated proliferation and migration capacities. Finally, growth of xenografts originated from CSRP1-knockdown cells is inhibited comparing to the control ones.

Conclusions: Expression of CSRP1 is positively correlated with COAD progression, which can promote tumor growth and migration. Higher CSRP1 can is a novel independent prognostic factor of COAD.

Background: Cervical cancer is the second most common cancer among women worldwide. Extensive studies have shown that microRNAs (miRNA/miR) can regulate the formation, progression, and metastasis of cancer. The purpose of this study was to investigate the effect of miR-19-3p on the proliferation, invasion, and autophagy of cervical cancer cells and to explore the underlying mechanism.

Methods: SiHa and HeLa cells were transfected with miR-19-3p mimic and inhibitor. miR-19-3p and PTEN expression were detected using real-time quantitative PCR and western blot, respectively. The binding between miR-19-3p and PTEN was predicted using Targetscan7.2 and verified by a dual-luciferase reporter gene assay. The effects of miR-19-3p on cell invasion and proliferation were evaluated by Transwell assays and MTT, respectively. The effect of miR-19-3p on autophagy was observed using fluorescence microscopy.

Results: The expression of miR-19-3p in cervical cancer tissues and SiHa and HeLa cells was significantly upregulated, whereas the expression of PTEN was significantly downregulated. PTEN was one of the direct targets of miR-19-3p. The miR-19-3p mimic significantly reduced the apoptosis rate and autophagy and promoted cell proliferation and invasion of the SiHa and HeLa cells.

Conclusion: In summary, miR-19b-3p can target PTEN to regulate the proliferation, invasion, and autophagy of cervical cancer cells. Our findings indicate the potential of miR-19-3p as a target for cervical cancer treatment in the future.

Objective: This study aimed to identify circular RNA profiles (circRNAs) via high-throughput RNA sequencing and distinguish the differentially expressed (DE) circRNAs between stable and unstable plaques.

Methods: RNA sequencing was performed on unstable and stable carotid plaque samples obtained from patients with carotid artery stenosis. DE circRNAs were screened, and six DE circRNAs were verified using quantitative real-time PCR (qRT-PCR). Functional evaluation of the DE circRNAs was conducted via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.

Results: We screened 344 DE circRNAs in unstable plaques, consisting of 342 upregulated and 2 downregulated circRNAs. GO analysis showed that the host genes of the upregulated circRNAs were related to ER to Golgi transport vesicle membrane, endocytic vesicle membrane, and Ran GTPase binding. KEGG analysis revealed that the host genes of the upregulated circRNAs were primarily associated with protein processing in endoplasmic reticulum, lysine degradation, homologous recombination, epithelial cell signaling in Helicobacter pylori infection, and yersinia infection. The results of qRT-PCR verified three upregulated DE circRNAs and two downregulated DE circRNAs in unstable plaques.

Conclusion: Hsa-circ-0001523, hsa-circ-0008950, hsa-circ-0000571, hsa-circ-0001946, and hsa-circ-0000745 may be involved in regulating the stability of atherosclerotic plaques and serves as a therapeutic target for unstable plaques.

Introduction: As the most malignant type of gliomas, glioblastoma is characterized with disappointing prognosis. Here, we aimed to investigate expression and function of NKD inhibitor of Wnt signaling pathway 1 (NKD1), an antagonist of Wnt-beta-catenin signaling pathways, in glioblastoma.

Methods: The mRNA level of NKD1 was firstly retrieved from TCGA glioma dataset to evaluate its correlation with clinical characteristics and its value in prognosis prediction. Then, its protein expression level in glioblastoma was tested by immunohistochemistry staining in a retrospectively cohort collected from our medical center (n = 66). Univariate and multivariate survival analyses were conducted to assess its effect on glioma prognosis. Two glioblastoma cell lines, U87 and U251, were used to further investigate the tumor-related role of NKD1 through overexpression strategy in combination with cell proliferation assays. Immune cell enrichment in glioblastoma and its correlation with NKD1 level was finally assessed using bioinformatics analyses.

Results: NKD1 shows a lower expression level in glioblastoma compared to that in the normal brain or other glioma subtypes, which is independently correlated to a worse prognosis in both the TCGA cohort and our retrospective cohort. Overexpressing NKD1 in glioblastoma cell lines can significantly attenuate cell proliferation. In addition, expression of NKD1 in glioblastoma is negatively correlated to the T cell infiltration, indicating it may have crosstalk with the tumor immune microenvironment.

Conclusions: NKD1 inhibits glioblastoma progression and its downregulated expression indicates a poor prognosis.

Background: Fetal growth restriction (FGR) is the impairment of the biological growth potential of the fetus and often leads to adverse pregnancy outcomes. The molecular mechanisms for the development of FGR, however, are still unclear. The purpose of this study is to identify critical genes associated with FGR through an integrated bioinformatics approach and explore the potential pathogenesis of FGR.

Methods: We downloaded FGR-related gene microarray data, used weighted gene co-expression network analysis (WGCNA), differentially expressed genes (DEGs), and protein-protein interaction (PPI) networks to screen hub genes. The GSE24129 gene set was used for validation of critical gene expression levels and diagnostic capabilities.

Results: A weighted gene co-expression network was constructed, and 5000 genes were divided into 12 modules. Of these modules, the blue module showed the closest relationship with FGR. Taking the intersection of the DEGs and genes in the blue module as pivotal genes, 277 genes were identified, and 20 crucial genes were screened from the PPI network. The GSE24129 gene set verified the expression of 20 genes, and CXCL9, CXCR3, and ITGAX genes were identified as actual pivotal genes. The expression levels of CXCL9, CXCR3, and ITGAX were increased in both the training and validation sets, and ROC curve validation revealed that these three pivotal genes had a significant diagnostic ability for FGR. Single-gene GSEA results showed that all three core genes activated "hematopoietic cell lineage" and "cell adhesion molecules" and inhibited the "cGMP-PKG signaling pathway" in the development of FGR. CXCL9, CXCR3, and ITGAX may therefore be closely associated with the development of FGR and may serve as potential biomarkers for the diagnosis and treatment of FGR.

Background: The problem of prognostic stratification in acute myeloid leukemia (AML) patients still has limitations.

Methods: The expression profile data and clinical features of AML patients were obtained from multiple publicly available sources, including GSE71014, TCGA-LAML, and TARGET-AML. Single-cell analysis was performed using the TISCH project. All the analysis was conducted in the R software.

Results: In our study, three public AML cohorts, GSE71014, TARGET-AML, and TCGA-AML, were selected. Then, we identified the prognosis-related molecules through bioinformatic analysis. Finally, the DUSP7 was noticed as a risk factor for AML patients, which has not been reported previously. Biological enrichment analysis and immune-related analysis were performed to illustrate the role of DUSP7 in AML. Single-cell analysis indicated that the DUSP7 was widely distributed in various cells, especially in monocyte/macrophages and malignant. Following this, a prognosis model based on DUSP7-derived genes was constructed, which showed a good prognosis prediction ability in all cohorts.

Conclusions: Our results preliminarily reveal the role and potential mechanism of DUSP7 in AML, providing direction for future research.

Immunoregulation is crucial to septic shock (SS) but has not been clearly explained. Our aim was to explore potential biomarkers for SS by pathway and transcriptional analyses of immune-related genes to improve early detection. GSE57065 and GSE95233 microarray data were used to screen differentially expressed genes (DEGs) in SS. Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses of DEGs were performed, and correlations between immune cell and pathway enrichment scores were analyzed. The predictive value of candidate genes was evaluated by receiver operating characteristic (ROC) curves. GSE66099, GSE4607, and GSE13904 datasets were used for external validation. Blood samples from six patients and six controls were collected for validation by qRT-PCR and western blotting. In total, 550 DEGs in SS were identified; these genes were involved in the immune response, inflammation, and infection. Immune-related pathways and levels of infiltration of CD4 + TCM, CD8 + T cells, and preadipocytes differed between SS cases and controls. Seventeen genes were identified as potential biomarkers of SS (areas under ROC curves >0.9). The downregulation of CD8A, CD247, CD3G, LCK, and HLA-DRA in SS was experimentally confirmed. We identified several immune-related biomarkers in SS that may improve early identification of disease risk.

Ovarian metastasis of gastric cancer indicates that the disease has reached the late stage and the opportunity for radical surgery is restricted. However, the clinical characteristics and prognosis of patients with gastric cancer ovarian metastasis (GCOM) remain to be illustrated. Here, we retrieved the information of 780 GCOM cases from the Surveillance, Epidemiology, and End Results (SEERs) database and analyzed their clinicopathological characteristics as well as their survival. According to our data, most GCOM patients showed poor pathological differentiation, advanced T and N stages. The prognostic factors include patients' age, tumor size, surgical resection, and chemotherapy treatment. Of note, the marriage status was also identified as an independent prognostic factor. Besides the identification of prognostic factors, we established nomograms to help predict the overall survival and cancer-specific survival of GCOM, respectively.

Background: PANoptosis has been a research hotspot, but the role of PANoptosis in hepatocellular carcinoma (HCC) remains widely unknown. Drug resistance and low response rate are the main limitations of chemotherapy and immunotherapy in HCC. Thus, construction of a prognostic signature to predict prognosis and recognize ideal patients for corresponding chemotherapy and immunotherapy is necessary.

Method: The mRNA expression data of HCC patients was collected from TCGA database. Through LASSO and Cox regression, we developed a prognostic signature based on PANoptosis-related genes. KM analysis and ROC curve were implemented to evaluate the prognostic efficacy of this signature, and ICGC and GEO database were used as external validation cohorts. The immune cell infiltration, immune status, and IC50 of chemotherapeutic drugs were compared among different risk subgroups. The relationships between the signature and the efficacy of ICI therapy, sorafenib treatment, and transcatheter arterial chemoembolization (TACE) therapy were investigated.

Result: A 3-gene prognostic signature was constructed which divided the patients into low- and high-risk subgroups. Low-risk patients had better prognosis, and the risk score was proved to be an independent predictor of overall survival (OS), which had a well predictive effect. Patients in high-risk population had more immunosuppressive cells (Tregs, M0 macrophages, and MDSCs), higher TIDE score and TP53 mutation rate, and elevated activity of base excision repair (BER) pathways. Patients with low risk benefited more from ICI, TACE, and sorafenib therapy. The predictive value of the risk score was comparable with TIDE and MSI for OS under ICI therapy. The risk score could be a biomarker to predict the response to ICI, TACE, and sorafenib therapy.

Conclusion: The novel signature based on PANoptosis is a promising biomarker to distinguish the prognosis predict the benefit of ICI, TACE, and sorafenib therapy, and forecast the response to them.

Background: Calcific aortic valve disease (CAVD) is the most common native valve disease. Valvular interstitial cell (VIC) osteogenic differentiation and valvular endothelial cell (VEC) dysfunction are key steps in CAVD progression. Circular RNA (circRNAs) is involved in regulating osteogenic differentiation with mesenchymal cells and is associated with multiple disease progression, but the function of circRNAs in CAVD remains unknown. Here, we aimed to investigate the effect and potential significance of circRNA-miRNA-mRNA networks in CAVD.

Methods: Two mRNA datasets, one miRNA dataset, and one circRNA dataset of CAVD downloaded from GEO were used to identify DE-circRNAs, DE-miRNAs, and DE-mRNAs. Based on the online website prediction function, the common mRNAs (FmRNAs) for constructing circRNA-miRNA-mRNA networks were identified. GO and KEGG enrichment analyses were performed on FmRNAs. In addition, hub genes were identified by PPI networks. Based on the expression of each data set, the circRNA-miRNA-hub gene network was constructed by Cytoscape (version 3.6.1).

Results: 32 DE-circRNAs, 206 DE-miRNAs, and 2170 DE-mRNAs were identified. Fifty-nine FmRNAs were obtained by intersection. The KEGG pathway analysis of FmRNAs was enriched in pathways in cancer, JAK-STAT signaling pathway, cell cycle, and MAPK signaling pathway. Meanwhile, transcription, nucleolus, and protein homodimerization activity were significantly enriched in GO analysis. Eight hub genes were identified based on the PPI network. Three possible regulatory networks in CAVD disease were obtained based on the biological functions of circRNAs including: hsa_circ_0026817-hsa-miR-211-5p-CACNA1C, hsa_circ_0007215-hsa-miR-1252-5p-MECP2, and hsa_circ_0007215-hsa-miR-1343-3p- RBL1.

Conclusion: The present bionformatics analysis suggests the functional effect for the circRNA-miRNA-mRNA network in CAVD pathogenesis and provides new targets for therapeutics.