Bioinformatics Identification and Experimental Validation of a Prognostic Model for the Survival of Lung Squamous Cell Carcinoma Patients.

Lung squamous cell carcinoma (LUSC) kills more than four million people yearly. Creating more trustworthy tumor molecular markers for LUSC early detection, diagnosis, prognosis, and customized treatment is essential. Cuproptosis, a novel form of cell death, opened up a new field of study for searching for trustworthy tumor indicators. Our goal was to build a risk model to assess drug sensitivity, monitor immune function, and predict prognosis in LUSC patients. The 19 cuproptosis-related genes were found in the literature, and patient genomic and clinical information was collected using the Cancer Genomic Atlas (TCGA) database. The LUSC patients were grouped using unsupervised clustering techniques, and 7626 differentially expressed genes were identified. Using univariate COX analysis, LASSO regression analysis, and multivariate COX analysis, a prognostic model for LUSC patients was developed. The tumor immune escape was evaluated using the Tumor Immune Dysfunction and Exclusion (TIDE) method. The R packages 'pRRophetic,' 'ggpubr,' and 'ggplot2' were utilized to examine drug sensitivity. For modeling, a 6-cuproptosis-based gene signature was found. Patients with high-risk LUSC had significantly worse survival rates than those with low-risk conditions. The possibility of tumor immunological escape was increased in patients with higher risk scores due to more immune cell inactivation. For patients with high-risk LUSC, we discovered seven potent potential drugs (AZD6482, CHIR.99021, CMK, Embelin, FTI.277, Imatinib, and Pazopanib). In conclusion, the cuproptosis-based genes predictive risk model can be utilized to predict outcomes, track immune function, and evaluate medication sensitivity in LUSC patients.

MiR-1976/NCAPH/P65 axis inhibits the malignant phenotypes of lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a malignancy with an abysmal survival rate. High metastasis is the leading cause of the low survival rate of LUAD. NCAPH, an oncogene, is involved in the carcinogenesis of LUAD. However, the regulation of NCAPH in LUAD remains controversial. In this work, we identified an up-regulation of NCAPH in LUAD tissues. Patients who expressed more NCAPH had shorter overall survival (OS). Furthermore, NCAPH overexpression promoted LUAD cell migration while inhibiting apoptosis. MiR-1976 and miR-133b were predicted to target NCAPH expression by searching TargetScan and linkedomics databases. Following that, we confirmed that miR-1976 suppressed NCAPH by directly targeting a 7-bp region of NCAPH 3' untranslated regions (UTR). In addition, increased expression of miR-1976 decreased the proliferation & migration and promoted apoptosis of LUAD cells, and the re-introduction of NCAPH reversed these influences. Furthermore, the xenograft and metastasis mouse models also confirmed that miR-1976 inhibited tumor growth and metastasis in vivo by targeting NCAPH. Finally, we found that MiR-1976 targeting NCAPH blocked the activation of NF-κB. In conclusion, miR-1976 inhibits NCAPH activity in LUAD and acts as a tumor suppressor. The miR-1976/NCAPH/NF-κB axis may, in the future, represent crucial diagnostic and prognostic biomarkers and promising therapeutic options.

A five-cuproptosis-related LncRNA Signature: predicting prognosis, assessing immune function & drug sensitivity in lung squamous cell carcinoma.

Lung squamous cell carcinoma has so far lacked effective targets for diagnosis and treatment. In cancer research, long noncoding RNAs (LncRNAs) emerge as novel therapeutic targets and biomarkers. Cuprophosis is a new death type involving multiple biological processes in tumor cells. Here, we aimed to explore whether Cuprophosis-related lncRNAs could be used to predict prognosis, assess immune function, and test drug sensitivity in LUSC patients. The Cancer Genome Map (TCGA) was used to obtain genome and clinical data, and Cuprophosis-relevant genes were found in the literature. A cuproptosis-related lncRNA risk model was built using co-expression analysis, univariate/multivariate Cox regression, and LASSO analysis. The survival analysis was used to assess the model's prognostic value. The univariate and multivariate Cox regression analyses were performed to determine whether risk score, age, gender, or clinical stages could be used as independent prognostic factors. Gene Set Enrichment Analysis and mutation analysis were performed on differentially expressed mRNA between high-risk and low-risk groups. The (TIDE) algorithm was used to conduct immunological functional analysis and drug sensitivity testing. Five cuproptosis-related LncRNAs were identified, and the selected LncRNAs constructed a prognosis model. According to the Kaplan-Meier survival analysis, the overall survival time for patients in the high-risk group was shorter than for those in the low-risk group. For LUSC patients, the risk score serves as an independent prognostic indicator. The GO and KEGG enrichment analysis revealed that the differentially expressed mRNAs between the high- and low-risk groups were enriched in several immune-related processes. The enrichment score of differentially expressed mRNAs in the high-risk group is higher than that of the low-risk group in multiple immune function pathways, including the IFN-γ and MHC I pathways. The Tumor Immune Dysfunction and Exclusion (TIDE) test revealed that the high-risk group was more likely to experience immune escape. The drug sensitivity analysis showed that patients with low-risk ratings were likely to respond to GW441756 and Salubrinal. In contrast, patients with higher risk scores were more responsive to dasatinib and Z-LLNIe CHO. The 5-Cuprophosis-related lncRNA signature can be used to predict prognosis, assess immune function, and test drug sensitivity in LUSC patients.

The polymerase δ-interacting protein family and their emerging roles in diseases.

The polymerase δ-interacting protein (POLDIP) family is a new family that can interact with DNA polymerase δ (delta). The members of the POLDIP family include POLDIP1, POLDIP2, and POLDIP3. Screened by the two-hybrid method, POLDIP1, POLDIP2, and POLDIP3 were initially discovered and named for their ability to bind to the p50 subunit of DNA polymerase δ. Recent studies have confirmed that POLDIPs are involved in the regulation of signal transduction pathways in neurodevelopment, neuropsychiatric diseases, cardiovascular diseases, tumors, and other diseases. However, each protein participates in different signaling pathways. In this review, we elucidate upon the family in terms of their genes and protein structures, their biological functions, in addition to the pathways that they are involved in during the development of diverse diseases. Finally, to provide new insights to the scientific community, we used the TCGA database to analyze and summarize the gene expressions of POLDIP family members in various tumors, as well as the correlations between their expressions and the overall survival times of tumor patients. Our data summary will give researchers working on cancer new concepts.

POU4F3 Acts as a Tumor Suppressor in Lung Adenocarcinoma via the Endoplasmic Reticulum Stress Signaling Pathway.

Lung cancer is the most common malignancy worldwide, and LUAD is the primary type of lung cancer. Recently, the POU transcription factor family has been associated with the development of multicancer, especially lung cancer. However, the relationship between POU domain class Ⅳ transcription factor Ⅲ (POU4F3) and lung cancer remains unknown. We detected the expression of POU4F3 in human LUAD and adjacent tissues with immunohistochemical staining, and we found that POU4F3 was expressed less in LUAD tissues compared with adjacent tissues. Patients with higher POU4F3 expression have more prolonged overall survival. We then constructed SPCA1 and A549 cells with stable overexpression or inhibition of POU4F3. We found that overexpressed POU4F3 suppressed LUAD cell proliferation in vitro and in vivo, according to CCK-8, colony formation, and xenograft assays. LUAD cell apoptosis was suppressed by POU4F3 overexpression based on Flow cytometry. The downregulation of POU4F3 yielded the opposite patterns. Next, we explored the possible mechanisms through which POU4F3 promoted the apoptosis of LUAD cells. Western blotting suggested that overexpression of POU4F3 significantly increased protein expression levels of the PERK/eIF2α/ATF4/CHOP and IRE1α/XBP1s pathways of ERS, while POU4F3 absence reversed the expressions of the above essential proteins in ERS pathways in SPCA1 and A549 cells. However, we found that PERK inhibitor but not IRE1 inhibitor can reverse the effect of POU4F3 overexpression on apoptosis. This study indicated that POU4F3 may work as a tumor suppressor in LUAD via regulating the PERK/eIF2α/ATF4/CHOP pathway. We made it possible to develop POU4F3 as a diagnostic, therapeutic, and prognostic target of LUAD.