Background Plasmacytoma variant translocation 1 (PVT1) is recognized as an oncogenic long non-coding RNA (lncRNA) in multiple cancer types including breast cancer (BC). Estrogen receptor alpha-positive (ERα+) BC is the major BC subtype, accounting for about 70% of cases. However, the role of PVT1 in this subtype and the underlying mechanisms are not yet fully elucidated. Objective To investigate the clinical significance and biological function of PVT1 in ERα+ BC. Methods The expression level and prognosis significance of PVT1 in ERα+ BC was explored through in silico analysis based on public databases. The biological function of PVT1 in ERα+ BC was examined in MCF7, a typical ERα+ BC cell line. MTS, plate clone formation and EdU assay were used to detect the effect of PVT1 knockdown on BC cell proliferation. The impact of PVT1 knockdown on estrogen signaling was assessed by measuring the expression of ERα and its downstream molecules through quantitative real-time PCR (qRT-PCR) and/or western blot. The regulatory effect of PVT1 on ERα was further investigated using protein stability experiments. To confirm the role of ERα in PVT1-regulated cell proliferation, rescue assay was conducted by targeting its downstream molecule BTG2. Results PVT1 expression is elevated in BC tissues compared to adjacent non-cancerous tissues, particularly in the ERα+ subtype. PVT1 knockdown substantially inhibited the proliferation of MCF7 cells as well as the estrogen signaling, which was evidenced by the marked downregulation of ERα and its downstream molecules including TFF1 and GREB1. Mechanistically, PVT1 knockdown was proved to significantly accelerate the degradation of ERα protein. BTG2 is a downstream molecule negatively regulated by ERα, which was upregulated upon PVT1 knockdown. In the rescue assay, interference of BTG2 could largely attenuated the inhibitory effect of PVT1 knockdown on cell proliferation. Conclusion PVT1 knockdown could inhibit cell proliferation partly through disrupting the ERα-BTG2 axis in ERα+ breast cancer.

Epithelial ovarian cancer (EOC) is a gynecological malignancy associated with high mortality, largely due to frequent diagnosis at advanced stages resulting from its asymptomatic early presentation. Although several single nucleotide polymorphisms (SNPs) have been implicated in EOC risk, its genetic determinants remain incompletely characterized. This study aimed to investigate the association between IGF2 polymorphisms (rs1004446, rs10840447, rs11602347, and rs4244808) and both susceptibility and clinicopathological characteristics of EOC in a Chinese population. Genomic DNA was extracted from peripheral whole blood samples. The four candidate SNPs in IGF2 were genotyped in 213 EOC patients (211 serous) and 203 healthy controls using the MassARRAY platform. The genotype frequencies of rs11602347 C > G (P < 0.0001) and rs4244808 T > G (P = 0.010) differed significantly between cases and controls. Genetic model analyses revealed that the rs11602347 C > G variant was associated with a reduced risk of EOC under dominant and additive models (CG + GG vs. CC: adjusted OR = 0.09, Benjamini-Hochberg adjusted P = 0.002; GG vs. CC: adjusted OR = 0.11, Benjamini-Hochberg adjusted P = 0.008), while the rs4244808 T > G variant was correlated with an increased risk under the recessive model (GG vs. TG + TT: adjusted OR = 2.51, Benjamini-Hochberg adjusted P = 0.016). Stratified analysis indicated that the protective effect of rs10840447 GG genotype was more pronounced in younger individuals (age ≤ 47: adjusted OR = 0.47, P = 0.028), whereas the TG + TT genotypes of rs4244808 were associated with significantly elevated EOC risk in older individuals (age > 47 :adjusted OR = 3.52, P = 0.015). Furthermore, among EOC cases, the GG genotype of rs11602347 was associated with an increased odds of advanced FIGO stage (III+IV vs. I+II: adjusted OR = 2.67, P = 0.034), while the GG genotype of rs4244808 was linked to a reduced odds of advanced FIGO stage (III + IV vs. I+ II: adjusted OR = 0.30, P = 0.032). Haplotype analysis showed that the GGGG* haplotype (rs1004446/rs10840447/rs11602347/rs4244808) was associated with an increased risk of EOC (OR = 2.16, P = 0.036). These findings provide preliminary evidence that IGF2 gene polymorphisms may be associated with the risk and clinicopathological characteristics of serous EOC in Chinese women.

BACKGROUND: Colorectal cancer (CRC) ranks high in both global incidence and mortality rates. The discovery of potential biomarkers and therapeutic targets can effectively improve early diagnosis, treatment efficacy, and prognosis for CRC patients. METHODS: Genes that were abnormally expressed in CRC tumors and associated with patients’ prognosis were first screened in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases; Clinical CRC samples were used to validate the results. The correlation between clinical characteristics and candidate genes, as well as their role in CRC cell proliferation, migration, invasion capability, and the cell cycle were analyzed. RESULTS: The study indicated that glycerol-3-phosphate dehydrogenase 1-like (GPD1L) was significantly down-regulated in CRC tumor tissues and served as an independent prognostic factor for OS and RFS of CRC patients. It was also associated with TNM staging, lymph node metastasis, tumor size, and tumor location. Inhibiting GPD1L expression significantly up-regulated the proliferation, migration, and invasion capabilities of CRC cells. CONCLUSIONS: GPD1L may serve as a prognostic biomarker for patients with CRC and participate in the regulation of CRC cell proliferation, migration, and invasion capability.

Breast cancer (BC) is a malignant tumor seriously threatening women’s health, while current approaches to BC treatment are challenged by the existence of drug resistance. Combination strategies of targeted therapy have been successfully applied in clinical BC treatment. However, whether there exist critical long non-coding RNAs (lncRNAs) responsible for BC pathogenesis and representing promising candidates for combined targeted therapy remains an issue. Public databases and bioinformatic methods were used to identify lncRNAs abnormally expressed among different subtypes of BC. The expression level of PVT1 was verified in collected clinical samples and representative cell lines. The role of PVT1 in BC cell proliferation was examined using MTS, plate clone formation, EdU and flow cytometry assay after small interfering RNA (siRNA) treatment. RNA sequencing was performed to investigate the potential molecular events regulated by PVT1. Western blot and immunofluorescence experiments were used to verify the activation of LATS2/Hippo signaling pathway after PVT1 knockdown. In addition, its activation was confirmed to mediate PVT1 function through rescue assay. The regulatory effect of PVT1 on LATS2 was investigated using mRNA stability experiments. The expression level of PVT1 in BC tissues of luminal and basal-like subtypes was significantly higher than that in paracancerous tissues. PVT1 knockdown substantially inhibited the proliferation of BC cells in both subtypes. RNA sequencing revealed that Hippo signaling pathway might be the downstream target of PVT1. After PVT1 knockdown, both mRNA and protein levels of LATS2 were elevated which further decreased the distribution of YAP in cell nucleus, indicating the activation of Hippo signaling pathway. The proliferation inhibitory effect of PVT1 could be attenuated by simultaneous knockdown of LATS2. Furthermore, knockdown of PVT1 was demonstrated to significantly slow down the degradation rate of LATS2 mRNA. PVT1 level was significantly elevated in luminal and basal-like BC subtypes. Knockdown of PVT1 could inhibit cell proliferation of these two BC subtypes partly through activating LATS2/Hippo signaling pathway.

Senescence, defined by the cessation of cell proliferation, plays a critical and multifaceted role in breast cancer progression and treatment. Senescent cells produce senescence-associated secretory phenotypes (SASP) comprising inflammatory cytokines, chemokines, and small molecules, which actively shape the tumor microenvironment, influencing cancer development, progression, and metastasis. This review provides a comprehensive analysis of the types and origins of senescent cells in breast cancer, alongside their markers and detection methods. Special focus is placed on pharmacological strategies targeting senescence, including drugs that induce or inhibit senescence, their molecular mechanisms, and their roles in therapeutic outcomes when combined with chemotherapy and radiotherapy. By exploring these pharmacological interventions and their impact on breast cancer treatment, this review underscores the potential of senescence-targeting therapies to revolutionize breast cancer management.

Mendelian Randomization (MR) analysis can link the host gut microbiome to cardiovascular diseases. Streptococcus anginosus (S. anginosus) has been found to be positively correlated with early atherosclerosis, but its role in lipid metabolism remains to be explored. To investigate the impact of S. anginosus on lipid metabolism, we employed M methods using large-scale population genome-wide association study (GWAS) sequencing data, combined with a C57BL/6J mouse obesity model to assess the role of S. anginosus in lipid metabolism. Throughout the entire experiment, we monitored the dynamic changes in serum blood lipids in mice and the abundance of S. anginosus in feces. We evaluated the accumulation of lipid droplets in the liver and adipose tissue, as well as examined the gene-level expression changes of lipid metabolism enzymes and transcription factors. The findings from MR analysis indicate that ten specific gut microbial taxa including Streptococcaceae exhibit a causal relationship with disorders of lipoprotein metabolism. Notably, Streptococcaceae has been identified as a risk factor for it. Furthermore, S. anginosus has been shown to elevate serum triglycerides (TG) levels, diminish the accumulation of lipid droplets in both hepatic and adipose tissues, and downregulate the gene expression of enzymes involved in TG synthesis and metabolism. These findings suggest that S. anginosus is a risk factor for lipoprotein disorders and reduces dietary lipid metabolism in a mouse obesity model, leading to TG metabolism dysfunction. This study combines bioinformatics analysis and animal experiments to provide new insights into S. anginosus as a risk factor for lipid metabolism disorders.

Purpose This study aimed to evaluate the prognostic role of the baseline neutrophil/lymphocyte ratio (NLR) in HER2-positive metastatic breast cancer (MBC) patients treated with trastuzumab/pertuzumab. Experimental design Data from 780 patients from the CLEOPATRA trial and 248 local patients were collected. Patients were divided into the low and high NLR subgroups by the NLR cutoff value. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) methods were used to control bias. Associations between the NLR and progression-free survival (PFS) and overall survival (OS) were analyzed. Results The baseline characteristics of the subgroups were well balanced after PSM and IPTW. A low baseline NLR was associated with better PFS and OS in the trastuzumab and docetaxel (TH) group in the unadjusted, PSM and IPTW models. After IPTW, a low NLR, versus a high NLR, was associated with improved PFS (HR 1.35, 95% CI 1.07–1.70, P = 0.012) and OS (HR 1.47, 95% CI 1.12–1.94, P = 0.006) in the TH group. In patients undergoing treatment with trastuzumab and pertuzumab and docetaxel (THP), a low baseline NLR was also correlated with better PFS but not OS across the three models. After IPTW, a low NLR was associated with better PFS (HR 1.52, 95% CI 1.20–1.93, P = 0.001) than a high NLR in the THP group. Multivariate analyses showed that a low baseline NLR was a predictor for PFS and OS in the TH group and for PFS in the THP group in all three models. In the real-world setting, a low baseline NLR was a predictor of better PFS among patients treated with docetaxel plus trastuzumab without or with pertuzumab in the multivariate model ( P = 0.015 and 0.008, respectively). Conclusions A low baseline NLR is associated with better survival outcomes among HER2-positive MBC patients receiving docetaxel plus trastuzumab/pertuzumab as first-line therapy.

Humans are exposed to various chemical elements that have been associated with the development and progression of diseases such as coronary artery disease (CAD). Unlike previous research, we employed a multi-element approach to investigate CAD patients and those with comorbid conditions such as diabetes (CAD-DM2), high blood pressure (CAD-HBP), or high blood lipids (CAD-HBL). Plasma concentrations of 21 elements, including lithium (Li), boron (B), aluminum (Al), calcium (Ca), titanium (Ti), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), strontium (Sr), cadmium (Cd), tin (Sn), stibium (Sb), barium (Ba), and lead (Pb), were measured in CAD patients (n = 201) and healthy subjects (n = 110) using inductively coupled plasma-mass spectrometry (ICP-MS). Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were utilized to analyze the ionomic profiles. Spearman correlation analysis was employed to identify the interaction patterns among individual elements. We found that levels of Ba, Li, Ni, Zn and Pb were elevated in the CAD group compared to the healthy group, while Sb, Ca, Cu, Ti, Fe, and Se were lower. Furthermore, the CAD-DM2 group exhibited higher levels of Ni and Cd, while the CAD-HBP group showed lower levels of Co and Mn. In the CAD-HBL group, Ti was increased, whereas Ba, Cr, Cu, Co, Mn, and Ni were reduced. In conclusion, ionomic profiles can be utilized to differentiate CAD patients from healthy individuals, potentially providing insights for future treatment or dietary interventions.

Background: The inhibitory effect of gamma 8T17 cells on the formation of murine malignant pleural effusions (MPE) has been established. However, there is limited understanding regarding the phenotypic characterization of gamma 8 T cells in MPE patients and their recruitment to the pleural cavity. Methods: We quantified gamma 8 T cell prevalence in pleural effusions and corresponding peripheral blood from malignant and benign patients using immunohistochemistry and flow cytometry. The expression of effector memory phenotype, stimulatory/inhibitory/chemokine receptors and cytokines on gamma 8 T cells in MPE was analyzed using multicolor flow cytometry. The infiltration of gamma 8 T cells in MPE was assessed through immunofluorescence, ELISA, flow cytometry and transwell migration assay. Results: We observed a significant infiltration of gamma 8 T cells in MPE, surpassing the levels found in blood and benign pleural effusion. gamma 8 T cells in MPE exhibited heightened expression of CD56 and an effector memory phenotype, while displaying lower levels of PD-1. Furthermore, gamma 8 T cells in MPE showed higher levels of cytokines (IFN-gamma, IL-17A and IL-22) and chemokine receptors (CCR2, CCR5 and CCR6). CCR2 expression was notably higher in the V82 subtype compared to V81 cells. Moreover, the complement C5a enhanced cytokine release by gamma 8 T cells, upregulated CCR2 expression in V82 subsets, and stimulated the production of chemokines (CCL2, CCL7 and CCL20) in MPE. In vitro utilizing CCR2 neutralising and C5aR antagonist significantly reduced the recruitment of gamma 8 T cells. Conclusions: gamma 8 T cells infiltrate MPE by overexpressing CCR2 and exhibit hightened inflammation, which is further augmented by C5a.

Bleeding is a major adverse event during clopidogrel treatment in patients with acute coronary syndrome (ACS). However, the potential mechanism affecting bleeding among individuals is unclear. Herein, we investigated the involvement of CYP2C19*2 and CYP2C19*3 , as well as 10 miRNA polymorphisms, in bleeding in Chinese patients with ACS during the first year of clopidogrel treatment. The miR-6076 rs1463411 G polymorphism was significantly associated with the risk of bleeding ( P < 0.001), and the rs1463411 GT + GG genotype significantly increased the risk of bleeding (adjusted odds ratio, 6.09; 95% confidence interval, 1.09–34.0; P < 0.001). Dual luciferase assay showed that miR-6076 significantly decreased the mRNA expression of P2RY12 ( P < 0.05). P2RY12 mRNA and protein levels were significantly lower in cells transfected with miR-6076-G than in cells transfected with miR-6076-T ( P < 0.05). The findings indicate that miR-6076 targets P2RY12 mRNA and that miR-6076 rs1463411 T/G polymorphisms differentially regulate P2RY12 mRNA and protein levels in cells. rs1463411 G polymorphism may increase the risk of bleeding during clopidogrel treatment in patients with ACS.

Long non-coding RNA (lncRNA) H19 is associated with proliferation, invasion and metastasis in numerous types of cancer. H19 lncRNA has been demonstrated to be an estrogen-inducible gene, the expression of which is significantly increased in tamoxifen (TAM)-resistant MCF-7 breast cancer cells. The aim of the present study was to investigate the role and molecular mechanism of lncRNA H19 in the development of TAM resistance. TAM-resistant MCF-7 (MCF-7R) cells were developed by the treatment of wild-type MCF-7 cells with 4-hydroxytamoxifen. Analysis of H19 expression in the cells indicated that upregulation of H19 contributed to the resistance of the MCF-7R cell line. Furthermore, when H19 was knocked down in the MCF-7R cells, the sensitivity to 4-hydroxytamoxifen was markedly restored. The results further demonstrated that N-acetyltransferase 1 (NAT1) may serve an important role in TAM-resistant cells, as NAT1 expression was notably downregulated in the MCF-7R cells but significantly elevated following the knockdown of H19. In addition, lower expression of NAT1 and higher expression of H19 were indicated to be associated with poor prognosis in patients with breast cancer treated with TAM. The results of bisulfite genomic sequencing PCR analysis indicated that the methylation rate of NAT1 in MCF-7R cells was significantly higher compared with that in MCF-7 cells, while the methylation rate of NAT1 in TAM-resistant cells transfected with small interfering RNA against H19 was significantly lower than that in the corresponding untransfected cells. Therefore, the present study suggests that the H19 gene regulates NAT1 expression in TAM-resistant cells via the mediation of NAT1 promoter methylation.

Glioblastoma multiforme (GBM) is a malignant cancer with severely poor survival, and the cells continue to thrive during hypoxia and toxic stress through autophagy. To validate the oncogenic role of long noncoding RNA H19 in GBM progression and examine whether autophagy and/or miR-491-5p participate in the process. The expression of H19 and autophagy-related genes in GBM and healthy control tissues was assessed via quantitative polymerase chain reaction. In addition, cell viability, proliferation, apoptosis and autophagy were respectively determined via cell counting kit-8 assay, clone formation assay, flow cytometry, western blotting and green fluorescent protein–microtubule-associated protein 1 light chain 3 alpha fluorescence analysis in vitro. Furthermore, a rescue assay was performed using rapamycin or miR-491-5p antagomir to examine the role of autophagy or miR-491-5p in H19-mediated regulation of proliferation and apoptosis. RNA pull-down and dual-luciferase reporter assays were employed to analyze the interaction between H19 and miR-491-5p. Additionally, tumor growth in a xenograft-bearing mouse model and autophagy in tumor mass were analyzed in vivo. The expression H19 was increased in GBM and was positively correlated with LC3 or Beclin-1. Silencing H19 inhibited growth and promoted apoptosis in GBM cells both in vitro and in vivo, and miR-491-5p was identified as one of the important mediators. H19 regulated the autophagy signaling pathway at least partly via miR-491-5p. Increased H19 expression in GBM exerts oncogenic effects by sponging miR-491-5p and enhancing autophagy. Therefore, H19 may be explored as a target for GBM therapy.

Introduction A major development in solid malignancy treatment is the application of immune checkpoint inhibitors (ICIs), which have produced durable responses and increased survival rates. However, the therapeutic effect of ICIs has great heterogeneity in patients with cancer. We propose a systematic review to evaluate the predictive value of tumour mutation burden (TMB) on efficacy of ICIs. Methods and analysis A systematic literature search will be conducted in the PubMed, OVID, Web of Science, Embase and Cochrane Central Register of Controlled Trials Library databases up to 31 May 2022. We will compare the efficacy of ICIs between TMB high group and TMB low group in terms of the HRs of overall survival (OS) and progression-free survival (PFS), and the OR of the objective response rate/overall response rate (ORR). The HRs of PFS and OS, and the OR of ORR, will be measured by an inverse variance weighted fixed effects model (I2≤50%) or a DerSimonian-Laird random effects model (I2>50%). In addition, subgroup analysis, sensitivity analysis, heterogeneity analysis and publication bias will be conducted. We plan to conduct a subgroup analysis on age, sex, area, number of patients (high/low TMB), cancer type, tumour size, stage, line of therapy, TMB sequencing method, type of immunotherapy and follow-up period. Ethics and dissemination Ethical approval and informed consent are not needed, as the study will be a literature review and will not involve direct contact with patients or alterations to patient care. This systematic review is anticipated to be finished in December 2023, and the results will be published in a peer-reviewed journal. PROSPERO registration number CRD42021262480.

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers, and long noncoding RNAs (lncRNAs) regulate gene expression or activities. This study investigated the role of lncRNA LINC00551 in ESCC development and progression. Three paired ESCC and normal tissues were subjected to next-generation sequencing and we identified 82 upregulated and 60 downregulated lncRNAs, including LINC00551, which was confirmed to markedly downregulated in 78 ESCC tissues and in the Gene Expression Profiling Interactive Analysis data set. Downregulated LINC00551 expression was associated with lymph node metastasis, advanced TNM stage, and tumor size. Moreover, downregulated LINC00551 expression was also associated with poor progression-free survival and overall survival of ESCC patients. In vitro and in vivo, LINC00551 overexpression inhibited ESCC cell proliferation and invasion, whereas knockdown of LINC00551 expression promoted ESCC cell proliferation and invasion. RNA pull-down and mass spectrometry assays identified the potential LINC00551 binding proteins, and HSP27 was a promising LINC00551 targeting proteins after RNA immunoprecipitation assay. At the protein level, LINC00551 bound to and decreased HSP27 phosphorylation, and in turn, downregulated ESCC cell proliferation and invasion. The current study demonstrated the functional significance of LINC00551 in ESCC development, progression, and prognosis. Further study will assess LINC00551 as a novel prognostic marker or therapeutic target for ESCC.

BACKGROUND:The essential roles of the tumor microenvironment (TME) have been recognized during the initiation and progression of primary lung adenocarcinoma (LUAD). The aim of the present study was to delineate the immune landscape in both primary cancer and matched lymph node metastasis from a cohort of locally advanced stage LUAD patients with distinct outcomes.METHODS:Formalin-fixed, paraffin-embedded samples were collected from 36 locally advanced LUAD patients. Transcriptome data of the tumor immune microenvironment were resolved using an immune oncology panel RNA sequencing platform. Bioinformatics approaches were used to determine the differentially expressed genes (DEGs), dysregulated pathways, and immune cell fraction between patients with early recurrence (ER) and late recurrence (LR).RESULTS:Here, we showed that in primary cancer tissues, 23 DEGs were obtained between patients with ER and LR. Functional analysis revealed that the LR in LUAD patients may be associated with enriched gene sets belonging to the antigen presentation and MHC protein complex, innate immune response, and IFN-γ signaling pathways. Next, the transcriptome data were adopted to quantify immune cell fractions, indicating that high infiltration of mast cells and neutrophils was correlated with ER. Interestingly, similar findings were observed in metastatic lymph nodes from patients suffering from ER or LR. By analyzing the shared immune features of primary cancers and lymphatic metastases, we unraveled the prognostic value and joint utility of two DEGs, CORO1A and S100A8.CONCLUSIONS:In LUAD, the enrichment in antigen presentation, MHC protein complex, and IFN-γ signaling, and low infiltration of neutrophils in primary or metastatic nodules may be indications for a favorable prognosis. Integrated with bioinformatics approaches, transcriptome data of immune-related genes from formalin-fixed, paraffin-embedded (FFPE) samples can effectively profile the landscape of the tumor immune microenvironment and help predict clinical outcomes.

To investigate the association between SNPs in human IGF2/H19 gene locus and epithelial ovarian cancer (EOC) risk, we performed a case-control study in 422 individuals (219 EOC patients and 203 cancer-free controls). Four SNPs (rs2525885, rs2839698, rs3741206, rs3741219) were found to be related with EOC risk. Specifically, the minor allele C of rs2525885 and allele A of rs2839698 was associated with elevated EOC genetic susceptibility under both dominant and recessive models (TC + CC vs TT: adjusted OR: 1.61, P = .031; CC vs TT + TC: adjusted OR: 4.87, P = .014; GA + AA vs GG: adjusted OR: 1.63, P = .023; AA vs GG + GA: adjusted OR: 2.43, P = .007). For rs3741206, the genotype TC + CC was associated with a significant decrease in EOC risk with the TT genotype as reference in a dominant genetic model (adjusted OR: 0.44, P = .003), while for rs3741219, genotype AA was associated with a 59% decrease in EOC risk only in the recessive model (adjusted OR: 0.41, P = .038). In the stratified analysis, an increased risk associated with the variant genotypes was observed in only subjects aged > 47 years for rs2525885 (adjusted OR = 2.04, P = .024), rs2839698 (adjusted OR = 2.50, P = .047) and rs3741206 (adjusted OR = 0.37, P = .009), respectively. What's more, the TC + CC genotype of rs2525885 was significantly associated with advanced FIGO stage (III vs II, adjusted OR = 2.73, P = .040).

Clopidogrel therapy reduces the occurrence of major vascular events in acute coronary syndrome (ACS) patients, but treatment efficacy is variable. The present study aims to determine the mechanisms that underlie associations between certain miRNA polymorphisms and clinical outcomes of clopidogrel therapy. Our study focused on 9 miRNA single nucleotide polymorphisms in addition to CYP2C19*2 and CYP2C19*3. We found that the miR-605 rs2043556 AG genotype significantly decreased the risk of acute myocardial infarction (odds ratio, OR = 0.13, 95%CI 0.02-0.96, P = .045) and that the rs2043556 GG genotype significantly decreased the risk of unstable angina (OR = 0.19, 95%CI 0.05-0.65, P = .008) in ACS patients receiving clopidogrel therapy for more than one year. Dual-luciferase analysis indicated that miR-605 significantly decreased the mRNA expression of CYP2B6 and P2RY12 (P < .01). In cells treated with miR-605-A, the protein and mRNA expression of CYP2B6 and P2RY12 were significantly lower than that of cells treated with miR-605-G (P < .05). The results demonstrate that miR-605 targets the mRNA of the CYP2B6 and P2RY12 genes, and that rs2043556 A/G polymorphisms in miR-605 modulate the mRNA and protein expression of CYP2B6 and P2RY12 differently, which may impact the effect of clopidogrel in ACS patients.

Esophageal squamous cell carcinoma (ESCC) is one of the most fatal malignancies of the digestive tract, but its underlying molecular mechanisms are not known. We aim to identify the genes involved in ESCC carcinogenesis and discover potential prognostic markers using integrated bioinformatics analysis. Three pairs of ESCC tissues and paired normal tissues were sequenced by high-throughput RNA sequencing (RNA-seq). Integrated bioinformatics analysis was used to identify differentially expressed coding genes (DECGs) and differentially expressed long non-coding RNA (lncRNA) genes (DELGs). A protein–protein interaction (PPI) network of DECGs was established using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) website and visualized with Cytoscape. Survival analysis was conducted by log-rank tests to identify “hub” genes with potential prognostic value, and real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was conducted to assess expression of these genes in ESCC tissues. TranswellTM assays were employed to examine the migration ability of cells after knockdown of LINC01614 expression, followed by investigation of epithelial–mesenchymal transition (EMT) by western blotting (WB). A total of 106 upregulated genes and 42 downregulated genes were screened out from the ESCC data sets. Survival analysis showed two hub protein-coding genes with higher expression in module 1 of the PPI network (SPP1 and BGN) and another three upregulated lncRNAs (LINC01614, LINC01415, NKILA) that were associated with a poor prognosis. High expression of SPP1, BGN, LINC01614, and LINC01415 in tumor samples was validated further by RT-qPCR. In vitro experiments show that knockdown of LINC01614 expression could significantly inhibit the migration of ESCC cells by regulating EMT, which was confirmed by WB. These results indicate that BGN, SPP1, LINC01614, and LINC01415 might be critical genes in ESCC and potential prognostic biomarkers.

Coronin 2A (CORO2A) is a novel component of the N-CoR (nuclear receptor co-repressor) complex. Abnormal CORO2A expression is associated with carcinogenesis. We used databases from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and analyzed CORO2A expression and gene regulation networks in breast cancer. Expression was analyzed using GEO and TCGA database and further validated in breast cancer samples collected in our clinic. The prognostic value of CORO2A was explored by using the Kaplan–Meier survival analysis and Cox proportional hazards regression analysis. LinkedOmics was used to identify coexpressed genes associated with CORO2A. After analyzing the intersection of coexpressed genes correlated with CORO2A and differentially expressed genes after CORO2A silencing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the intersecting genes were conducted by using FunRich software. Transwell assays were performed in breast cancer cells to determine the effect of CORO2A on cell migration. MTS, colony formation, and cell cycle distribution assays were performed in breast cancer cells to determine the effect of CORO2A on cell proliferation. Gene enrichment analysis was employed to explore the target networks of transcription factors and miRNAs. We found that CORO2A was upregulated and that the elevated expression of CORO2A was associated with poor overall survival (OS) and relapse-free survival (RFS) in TNBC patients. Further bioinformatics analysis of public sequencing data and our own RNA-Seq data revealed that CORO2A was probably involved in the epithelial-to-mesenchymal transition process and might have a significant effect on the migration of breast cancer cells, which might be mediated via pathways involving several miRNAs and MYC transcription factors. Functionally, the knockdown of CORO2A inhibited cell migration, decreased viability, and colony formation and induced cell cycle arrest in the G0/G1 phase in breast cancer cells. These results demonstrate that bioinformatics-based analysis efficiently reveals information about CORO2A expression and its potential regulatory networks in breast cancer, laying a foundation for further mechanistic research on the role of CORO2A in carcinogenesis. Moreover, CORO2A promotes the migration and proliferation of breast cancer cells and may have an important function in breast cancer progression. CORO2A is a potential prognostic predictor for TNBC patients. Targeting CORO2A may provide promising therapy strategies for breast cancer treatment.