MIS18A upregulation promotes cell viability, migration and tumor immune evasion in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) presents a significant global health challenge owing to its poor prognosis and high mortality rates. Despite its involvement in the initiation and progression of a number of cancer types, the understanding of the precise impact of MIS18 kinetochore protein A (MIS18A) on LUAD remains incomplete. In the present study, the role of MIS18A in LUAD was investigated by analyzing the genomic and clinical data from multiple public datasets. The expression of MIS18A was validated using reverse transcription-quantitative polymerase chain reaction, and in vitro experiments involving small interfering RNA-induced downregulation of MIS18A in lung cancer cells were conducted to further explore its impact. These findings revealed that elevated MIS18A expression in LUAD was associated with advanced clinical features and poor prognosis. Functional analysis also revealed the role of MIS18A in regulating the cell cycle and immune-related pathways. Moreover, MIS18A altered the immune microenvironment in LUAD, influencing its response to immunotherapy and drug sensitivity. The results of the in vitro experiments indicated that suppression of MIS18A expression reduced the proliferative and migratory capacities of LUAD cells. In summary, MIS18A possesses potential as a biomarker and may serve as a possible therapeutic target for LUAD, with significant implications for tumor progression by influencing both cell cycle dynamics and immune infiltration.

NEDD1 overexpression increases cell proliferation, tumor immune escape, and drug resistance in LUAD.

Background: Neural Precursor Cell Expressed Developmentally Down-Regulated Protein 1 (NEDD1) serves as a crucial factor in promoting cellular mitosis by directly facilitating wheel assembly and daughter centriole biogenesis at the lateral site of parent centrioles, ultimately driving centrosome replication. The amplification of centrosomes and the abnormal expression of centrosome-associated proteins contribute to the invasion and metastasis of non-small cell lung cancer cells. However, the specific mechanism by which NEDD1 contributes to the progression of lung adenocarcinoma (LUAD) remains unexplored. Therefore, the objective of this study is to uncover the role played by NEDD1 in LUAD. Methods: To verify the expression of NEDD1 in pan-carcinoma. The feasibility of NEDD1 as a prognostic marker for LUAD in TCGA and GEO databases was verified. Subsequently, Cox proportional hazard regression analysis was used to screen the prognostic factors of LUAD, so as to analyze the correlation between prognostic factors and NEDD1 expression. For another, NEDD1-related genes were screened for pathway enrichment analysis to verify their possible functions. In addition, the expression of NEDD1 in LUAD was verified by qPCR and IHC, then siRNA was used to construct NEDD1-knocked lung cancer cells for subsequent cytobehavioral experiments. Finally, the distribution of NEDD1 in single-cell samples was revealed, and then the correlation between its overexpression and LUAD immune escape and drug resistance was analyzed. Results: LUAD exhibits upregulation of NEDD1, which in turn promotes the proliferation, migration, invasion, and epithelial-mesenchymal transition of lung cancer cells, thereby contributing to a poor prognosis. Furthermore, the overexpression of NEDD1 is closely associated with immune escape and drug resistance in LUAD. Conclusion: NEDD1 serves as a reliable prognostic marker for LUAD, and its upregulation is associated with increased immune escape and drug resistance. Given these findings, NEDD1 holds potential as a novel therapeutic target for the treatment of LUAD.

Upregulation of POC1A in lung adenocarcinoma promotes tumour progression and predicts poor prognosis.

Lung adenocarcinoma (LUAD) is characterized by a high incidence rate and mortality. Recently, POC1 centriolar protein A (POC1A) has emerged as a potential biomarker for various cancers, contributing to cancer onset and development. However, the association between POC1A and LUAD remains unexplored. We extracted The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) data sets to analyse the differential expression of POC1A and its relationship with clinical stage. Additionally, we performed diagnostic receiver operator characteristic (ROC) curve analysis and Kaplan-Meier (KM) survival analysis to assess the diagnostic and prognostic value of POC1A in LUAD. Furthermore, we investigated the correlation between POC1A expression and immune infiltration, tumour mutation burden (TMB), immune checkpoint expression and drug sensitivity. Finally, we verified POC1A expression using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). Cell experiments were conducted to validate the effect of POC1A expression on the proliferation, migration and invasion of lung cancer cells. POC1A exhibited overexpression in most tumour tissues, and its overexpression in LUAD was significantly correlated with late-stage presentation and poor prognosis. The high POC1A expression group showed lower levels of immune infiltration but higher levels of immune checkpoint expression and TMB. Moreover, the high POC1A expression group demonstrated sensitivity to multiple drugs. In vitro experiments confirmed that POC1A knockdown led to decreased proliferation, migration, and invasion of lung cancer cells. Our findings suggest that POC1A may contribute to tumour development by modulating the cell cycle and immune cell infiltration. It also represents a potential therapeutic target and marker for the diagnosis and prognosis of LUAD.

Silencing of METTL3 inhibits m6A methylation of NEK7 to suppress pyrolysis in an HT-22 cell-based model of intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) induces severe neurological damage, and its progression is driven by METTL3. This study aimed to investigate the role of METTL3 in ICH via in vitro experiments. For this purpose, HT-22 cells were treated with hemin to mimic ICH in vitro, followed by evaluating cell pyroptosis using flow cytometry, lactic dehydrogenase release analysis, enzyme-linked immunosorbent assay, and western blotting. Moreover, N6-methyl adenosine (m6A) methylation of NEK7 was assessed using methylated RNA immunoprecipitation, RNA immunoprecipitation, dual-luciferase reporter assay, and quantitative real-time polymerase chain reaction. Results indicated that knockdown of METTL3 inhibited hemin-induced pyroptosis and suppressed m6A methylation of NEK7 due to METTL3 downregulation, reducing NEK7 mRNA stability. The effects on METTL3-induced cell pyroptosis were abrogated by overexpressing NEK7, while IGF2BP2 increased NEK7 expression. Similarly, IGF2BP2 silence downregulated NEK7 expression mediated by METTL3. In conclusion, silencing of METTL3 inhibited hemin-induced HT-22 cell pyroptosis by suppressing m6A methylation of NEK7, which was recognized by IGF2BP2. These findings are envisaged to identify a novel therapeutic strategy for ICH.

Effects of leucism on organ development and molecular mechanisms in Northern snakehead (Channa argus) beyond pigmentation alterations.

Leucism, a widespread occurrence observed in Northern snakehead (Channa argus), bestows a striking white jade-like body coloration upon affected individuals and has gained substantial popularity in commercial breeding. While the visible manifestation of leucism in snakeheads is primarily limited to body coloration, it is crucial to explore the potential influence of leucism on organ development and elucidate the underlying molecular mechanisms. Through a comparative analysis of growth differences, our study revealed that at 150 days post-fertilization, the white variety exhibited an 8.5% higher liver index and intestinal index, but experienced a 20% and 38% decreased in spleen index and renal interstitial index, respectively, suggesting an enlarged digestive area but relatively smaller immune tissues. Nonetheless, no significant differences were observed in the intestinal flora between the two varieties, suggesting the exclusion of any exogenous impacts from symbiotic flora on the growth and development of the white variety. Importantly, transcriptome analysis demonstrated that the white variety exhibited higher expression levels of innate immune genes. Furthermore, annotation of the gene sets expressed in the liver and spleen revealed 76 and 35 genes respectively, with the white variety displaying lower expression in genes associated with "Viral protein interaction with cytokine and cytokine receptor", "Protein processing in endoplasmic reticulum", and "TNF signaling pathway", while exhibiting higher expression in "Estrogen signaling pathway". Notably, three genes, namely pcdhf 4, nlrc3 card 15-like, and a pol-like were identified in both the liver and spleen, indicating their potential involvement in altering the development and innate immunity of the white variety. This study reveals the systemic impact of leucism that extends beyond mere pigmentation alterations, highlighting the prominent characteristics of this phenotype and providing a foundation for future molecular breeding programs aimed at enhancing this variety.

Effects of glucocorticoid use on survival of advanced non-small-cell lung cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: Lung cancer is the second most common cancer worldwide, with non-small-cell lung cancer (NSCLC) accounting for the majority of cases. Patients with NSCLC have achieved great survival benefits from immunotherapies targeting immune checkpoints. Glucocorticoids (GCs) are frequently used for palliation of cancer-associated symptoms, as supportive care for non-cancer-associated symptoms, and for management of immune-related adverse events (irAEs). The aim of this study was to clarify the safety and prognostic significance of glucocorticoid use in advanced patients with NSCLC treated with immune checkpoint inhibitors (ICIs). METHODS: The study searched publications from PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine disc, Chinese National Knowledge Infrastructure, Wanfang Data, and Chinese Science and Technology Journal Database up to March 1st, 2022, and conducted a meta-analysis to assess the effects of glucocorticoid use on overall survival (OS) and progression-free survival (PFS) in NSCLC patients treated with ICIs through the available data. The study calculated the pooled hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: This study included data from 25 literatures that were mainly retrospective, with 8713 patients included. Patients taking GCs had a higher risk for tumor progression and death compared with those not taking GCs (PFS: HR = 1.57, 95% CI: 1.33-1.86, P <0.001; OS: HR = 1.63, 95% CI: 1.41-1.88, P <0.001). GCs used for cancer-associated symptoms caused an obviously negative effect on both PFS and OS (PFS: HR = 1.74, 95% CI: 1.32-2.29, P <0.001; OS: HR = 1.76, 95% CI: 1.52-2.04, P <0.001). However, GCs used for irAEs management did not negatively affect prognosis (PFS: HR = 0.68, 95% CI: 0.46-1.00, P = 0.050; OS: HR = 0.53, 95% CI: 0.34-0.83, P = 0.005), and GCs used for non-cancer-associated indications had no effect on prognosis (PFS: HR = 0.92, 95%CI: 0.63-1.32, P = 0.640; OS: HR = 0.91, 95% CI: 0.59-1.41, P = 0.680). CONCLUSIONS: In advanced NSCLC patients treated with ICIs, the use of GCs for palliation of cancer-associated symptoms may result in a worse PFS and OS, indicating that they increase the risk of tumor progression and death. But, in NSCLC patients treated with ICIs, the use of GCs for the management of irAEs may be safe, and the use of GCs for the treatment of non-cancer-associated symptoms may not affect the ICIs' survival benefits. Therefore, it is necessary to be careful and evaluate indications rationally before administering GCs in individualized clinical management.

Analysis of Nucleoporin 107 Overexpression and Its Association with Prognosis and Immune Infiltration in Lung Adenocarcinoma by Bioinformatics Methods.

Background: Lung adenocarcinoma (LUAD) has high morbidity and mortality. Current studies indicate nucleoporin 107 (NUP107) is involved in the construction of nuclear pore complex, and NUP107 overexpression contributes to the growth and development in most types of cancers, but its effect in LUAD has not been elucidated. Methods: Differences in NUP107 expression were investigated using the Cancer Genome Atlas (TCGA) and multiple Gene Expression Omnibus (GEO) data sets. Enrichment analysis were implemented to probe the NUP107 function. The association of NUP107 with the degree of immune cell infiltration was investigated by the TIMER database, single-sample gene set enrichment analysis (ssGSEA), and ESTIMATE. The association of NUP107 expression with tumor mutation burden (TMB), TP53, and immune checkpoint was analyzed. Single-cell RNA sequencing data were used to detect NUP107 expression in different cell clusters. Finally, we performed real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) to prove the difference of NUP107 expression. Results: NUP107 was overexpressed in LUAD and mainly expressed in cancer stem cell (CSC). Overexpression of NUP107 in LUAD suggested a poorer prognosis. Functional enrichment analysis pointed out that NUP107 was mainly linked to the regulation of cell cycle. Both immune cell infiltration and TMB were found to be in connection with NUP107. Cases in the group with high NUP107 expression had poorer immune infiltration, but had higher expression of immune checkpoints, TMB, and proportion of TP53 mutations. Conclusion: NUP107 is a sensitive diagnostic and prognostic factor for LUAD and may be involved in tumor progression through its effects on cell cycle and immune infiltration.

High SGO2 predicted poor prognosis and high therapeutic value of lung adenocarcinoma and promoted cell proliferation, migration, invasion, and epithelial-to-mesenchymal transformation.

Background: Shugoshin 2 (SGO2), a component of the cell division cohesion complex, is involved in both mitotic and meiotic processes. Despite being overexpressed in various malignant tumors and is associated with poor prognosis, its exact role in lung adenocarcinoma (LUAD) and its biological effects on lung cancer cells are not well understood. Methods: The transcriptomics data and clinical information for LUAD were obtained from TCGA and GEO, and DEGs associated with prognostic risk factors were screened using Cox regression analysis and chi-square testing. Identify these gene functions using correlation heatmaps, protein interaction networks (PPIs), and KEGG enrichment assays. The expression of SGO2 in tissues was verified by PCR and IHC, and the prognostic value of SGO2 in LUAD was evaluated by survival analysis. In addition, the effects of SGO2 knockdown on lung cancer cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT) were studied in vitro. After that, the TIMER database and single-sample GSEA (ssGSEA) analysis were used to investigate the correlation between SGO2 and immune infiltration. Finally, the tumor mutational burden (TMB) of different SGO2 clusters and the efficacy of the two clusters in multiple treatments were evaluated. Results: High-risk genes associated with poor prognosis in LUAD are involved in cell cycle regulation and proliferation. Among these genes, SGO2 exhibited high expression in LUAD and corresponded with the TNM stage. Furthermore, the knockdown of SGO2 led to a decrease in the proliferation, migration, invasion, and EMT processes of lung cancer cells. Notably, high SGO2 expression may have poorer anti-tumor immunity and may therefore be more suitable for immunotherapy to re-establish immune function, while its high expression with a higher TMB could enable LUAD to benefit from multiple therapies. Conclusion: Our findings suggest that SGO2 may be a promising prognostic biomarker for LUAD, particularly in regulating the cell cycle and benefiting from multiple therapies.

LncRNA PCAT6 promotes proliferation, migration, invasion, and epithelial-mesenchymal transition of lung adenocarcinoma cell by targeting miR-545-3p.

BACKGROUND: Lung cancer is a high incidence cancer on a worldwide basis and has become a major public health problem. Lung adenocarcinoma (LUAD) makes up approximately half of all lung cancers and is a threat to human health. Long non-coding RNAs (lncRNAs) is an important regulator of the development and progression of lung adenocarcinoma. In this manuscript we examined the role and potential mechanism of lncRNA PCAT6 in the development of LUAD. METHODS AND RESULTS: Differences in lncRNA PCAT6 levels between LUAD samples and normal samples were first explored in the GEPIA database. We found that lncRNA PCAT6 expression was elevated, which was also validated in lung adenocarcinoma tissues and cell lines. Using western blotting, CCK-8, EdU, wound healing and transwell assays, we found that knockdown of lncRNA PCAT6 inhibited EMT, proliferation, migration, and invasion of LUAD cells. We noted a predicted a binding site for lncRNA PCAT6 and miR-545-3p through conducting bioinformatic analyses, and their binding was subsequently verified by a dual-luciferase reporter assay. Rescue experiments confirmed that miR-545-3p inhibitor partially abolished the inhibition function of lncRNA PCAT6 knockdown on LUAD cells. In addition, we predicted the downstream target genes of miR-545-3p and verified them by RT-qPCR. We found that EGFR was reduced in the silence of lncRNA PCAT6 and upregulated after miR-545-3p inhibition. CONCLUSION: This study demonstrates that lncRNA PCAT6 promotes a more aggressive LUAD phenotype by sponging miR-545-3p. This finding may provide new ideas for the treatment of lung cancer.

NCAPD2 is a novel marker for the poor prognosis of lung adenocarcinoma and is associated with immune infiltration and tumor mutational burden.

Lung adenocarcinoma (LUAD) is at present the most prevalent subtype of lung cancer worldwide. Non-SMC condensin I complex subunit D2 (NCAPD2) is one of the 3 non-SMC subunits in condensin I. Previous studies have confirmed that NCAPD2 plays a critical role in chromosome cohesion and segregation. NCAPD2 may be involved in tumorigenesis and progression by participating in abnormal cell cycle division, but the prognostic value of NCAPD2 in LUAD remains unclear. We investigated differences in the expression levels of NCAPD2 and determined their association with clinical features, as well as their diagnostic and prognostic value using the cancer genome atlas database. The function of NCAPD2 was analyzed using gene ontology, Kyoto encyclopedia of genes and genomes, and gene set enrichment analysis. CIBERSORT, single-sample gene set enrichment analysis, and ESTIMATE were used to analyze the immune microenvironment of tumor patients. Tumor mutational burden (TMB) and immune checkpoints were analyzed, while hub genes were identified using weighted gene coexpression network analysis and were used to construct prognostic models. Subsequently, the competing endogenous RNAs network of NCAPD2 in LUAD was explored. Finally, we performed qPCR to verify differences in NCAPD2 expression between the tumor and normal tissues. The expression of NCAPD2 in LUAD was significantly upregulated compared with normal lung tissues. NCAPD2 has been linked to the T stage, N stage, and tumor stage. The elevated expression of NCAPD2 in LUAD can predict a poor prognosis. Functional enrichment analysis indicated that the main function of NCAPD2 was in cell cycle regulation. Moreover, NCAPD2 was also associated with immune cell infiltration and TMB. NCAPD2 is a novel prognostic marker in LUAD and is associated with immune infiltration and TMB.

Long non-coding RNA FAM83A antisense RNA 1 (lncRNA FAM83A-AS1) targets microRNA-141-3p to regulate lung adenocarcinoma cell proliferation, migration, invasion, and epithelial-mesenchymal transition progression.

The current paper investigates how long non-coding RNA (lncRNA) FAM83A antisense RNA 1 (lncRNA FAM83A-AS1) affected the epithelial-mesenchymal transformation (EMT), growth, invasion and migration of lung adenocarcinoma (LUAD) via targeting miRNA-141-3p. The GEPIA and ENCORI databases were used to analyze differences in lncRNA FAM83A-AS1 levels within LUAD samples. FAM83A-AS1 and miR-141-3p levels were assessed using qRT-PCR among 30 LUAD samples and surrounding normal tissues. In addition, we analyzed how FAM83A-AS1 affected proliferation, invasion, migration, and EMT processes of LUAD cells by targeting miR-141-3p through EdU, CCK-8 assay, scratch assay, transwell migration and invasion assay, immunofluorescence (IF) staining and WB assay. MicroRNAs targeting FAM83A-AS1 were screened using AnnoLnc2 and identified by RT-qPCR. Dual-luciferase assays were utilized to evaluate the connection between FAM83A-AS1 and miR-141-3p. FAM83A-AS1 expression was remarkably raised in lung cancer cells and tissue samples; however, miR-141-3p level markedly reduced relative to healthy samples. FAM83A-AS1 silencing suppressed EMT, growth, invasion and migration of LUAD cells. MiR-141-3p was the possible FAM83A-AS1 binding target negatively associated with FAM83A-AS1. The miR-141-3p inhibitor partly abolished the FAM83A-AS1 knockdown-induced inhibition on EMT, cell growth, invasion and migration in LUAD cells. In addition, miR-141-3p down-regulation abolished the inhibition of E-box-bound zinc finger protein 1 and 2 protein production following FAM83A-AS1 knockdown. According to our results, FAM83A-AS1/miR-141-3p axis plays an important role in LUAD occurrence and development. FAM83A-AS1 sponged miR-141-3p to down-regulate the level of the latter within LUAD and thereby encouraging LUAD development and suggesting a possible novel therapeutic approach for LUAD.