Mogrol-mediated enhancement of radiotherapy sensitivity in non-small cell lung cancer: a mechanistic study.

This study investigated mogrol's impact on non-small cell lung cancer (NSCLC) radiosensitivity and underlying mechanisms, using various methods including assays, bioinformatics, and xenograft models. CCK-8, clonogenic, flow cytometry, TUNEL, and Western blot assays evaluated mogrol and radiation effects on NSCLC viability and apoptosis. Ubiquitin-specific protease 22 (USP22) expression in NSCLC patient tissues was determined by RT-qPCR and Western blot. A xenograft model validated mogrol's effects on tumor growth. Bioinformatics identified four ubiquitin-specific proteases, including USP22, in NSCLC. Kaplan-Meier analysis confirmed USP22's value in lung cancer survival. Human Protein Atlas (HPA) database analysis indicated higher USP22 expression in lung cancer tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis implicated ERK1/2 in NSCLC progression, and molecular docking showed stability between mogrol and ERK1/2. Further in vivo and in vitro experiments have demonstrated that mogrol enhances the inhibitory effect of radiation on NSCLC cell viability and clonogenic capacity. Cell viability and clonogenic capacity are reduced by >50%, and an increase in cellular apoptosis is observed, with apoptotic levels reaching 10%. USP22 expression was significantly elevated in NSCLC tissues, particularly in radiotherapy-resistant patients. Mogrol downregulated USP22 expression by inhibiting the ERK/CREB pathway, lowering COX2 expression. Mogrol also enhanced radiation's inhibition of tumor growth in mice. Mogrol enhances NSCLC radiosensitivity by downregulating USP22 via the ERK/CREB pathway, leading to reduced COX2 expression.NEW & NOTEWORTHY Mogrol enhances non-small cell lung cancer (NSCLC) cell sensitivity to radiotherapy by downregulating USP22 through the ERK/CREB pathway, reducing COX2 expression. These findings highlight mogrol's potential as an adjunct to improve NSCLC radiotherapy and open avenues for further research and clinical applications.

Up-Regulation of MELK Promotes Cell Growth and Invasion by Accelerating G1/S Transition and Indicates Poor Prognosis in Lung Adenocarcinoma.

Maternal embryonic leucine zipper kinase (MELK) is an oncogene in many tumors, although its contribution to lung adenocarcinoma (LUAD) is unclear. We examined MELK expression in patient LUAD tissue and matched healthy lung tissues. We investigated the connection between MELK expression and tumor differentiation, lymph node metastasis, and patient survival. We downregulated MELK expression using small-hairpin RNA to assess its impact on LUAD cell proliferation, clonogenicity, and invasion. We also investigated the molecular mechanism underlying these effects. MELK expression was significantly heightened in LUAD tissue as opposed to the matching healthy lung tissues. LUAD patients who had MELK overexpression had a worse prognosis. Suppression of MELK hinders proliferation, clonogenicity, and invasion of LUAD cells. The MELK suppression led to the arrest of the cell cycle's G1/S phase by reducing the cyclin E1 and cyclin D expression. Our outcomes manifest that MELK can function as a beneficial prognostic indication and a new therapy target for LUAD. MELK has an essential function in progressing LUAD, manifesting potential as a viable target for therapeutic intervention in this disease management.

Identification of WD-Repeat Protein 72 as a Novel Prognostic Biomarker in Non-Small-Cell Lung Cancer.

WD-repeat protein 72(WDR72; OMIM∗613214), a scaffolding protein lacking intrinsic enzymatic activity, produces numerous ß-propeller blade formations, serves as a binding platform to assemble protein complexes and is critical for cell growth, differentiation, adhesion, and migration. Despite evidence supporting a basic role of WDR72 in the tumorigenesis of particular cancers, the value of WDR72 in non-small-cell lung cancer (NSCLC), the tumor with the highest mortality rate globally, is undocumented. We investigated the prognostic value of WDR72 in NSCLC and studied its potential immune function and its correlation with ferroptosis. According to The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, Genotype-Tissue Expression, and Gene Set Cancer Analysis, we used multiple bioinformatic strategies to investigate the possible oncogenic role of WDR72, analyze WDR72 and prognosis, and immune cell infiltration in different tumors correlation. WDR72 exhibited a high expression in NSCLC and a positive association with prognosis. WDR72 expression was related to immune cell infiltration and tumor immune microenvironment in NSCLC. Finally, we validated WDR72 in human NSCLC; it has a predictive value in NSCLC related to its function in tumor progression and immunity. The significance of our study is that WDR72 can be used as a potential indicator of lung cancer prognosis. Helping physicians more accurately predict patient survival and risk of disease progression.

Frozen sections accurately predict the IASLC proposed grading system and prognosis in patients with invasive lung adenocarcinomas.

INTRODUCTION: The International Association for the Study of Lung Cancer (IASLC) newly proposed grading system for lung adenocarcinomas (ADC) has been shown to be of prognostic significance. Hence, intraoperative consultation for the grading system was important regarding the surgical decision-making. Here, we evaluated the accuracy and interobserver agreement for IASLC grading system on frozen section (FS), and further investigated the prognostic performance. METHODS: FS and final pathology (FP) slides were reviewed by three pathologists for tumor grading in 373 stage I lung ADC following surgical resection from January to June 2013 (retrospective cohort). A prospective multicenter cohort (January to June 2021, n = 212) were included to confirm the results. RESULTS: The overall concordance rates between FS and FP were 79.1% (κ = 0.650) and 89.6% (κ = 0.729) with substantial agreement in retrospective and prospective cohorts, respectively. Presence of complex gland was the only independent predictor of discrepancy between FS and FP (presence versus. absence: odds ratio, 2.193; P = 0.015). The interobserver agreement for IASLC grading system on FS among three pathologists were satisfactory (κ = 0.672 for retrospective cohort; κ = 0.752 for prospective cohort). Moreover, the IASLC grading system by FS diagnosis could well predict recurrence-free survival and overall survival for patients with stage I invasive lung ADC. CONCLUSIONS: Our results suggest that FS had high diagnostic accuracy and satisfactory interobserver agreement for IASLC grading system. Future prospective studies are merited to validate the feasibility of using FS to match patients into appropriate surgical type.

KDM2B mediates the Wnt/ß-catenin pathway through transcriptional activation of PKMYT1 via microRNA-let-7b-5p/EZH2 to affect the development of non-small cell lung cancer.

The significance of KDM2B in oncogenesis has been appreciated, but the mechanism behind is incompletely understood. In this work, we addressed its effects on the progression of non-small cell lung cancer (NSCLC). Overexpression of KDM2B was linked to dismal prognoses of NSCLC patients. Based on the expression levels of KDM2B in a panel of NSCLC cell lines, A549, showing lower level of expression, and SK-MES-1, showing higher levels of expression, were selected as model systems to evaluate the effect of KDM2B overexpression and KDM2B silencing, respectively. Knockdown of KDM2B hampered NSCLC cell proliferation, invasion, as well as migration, while enhanced apoptosis. Additionally, KDM2B repressed the expression of microRNA (miR)-let-7b-5p through demethylation modification of H3K36me2, thereby promoting the expression of zester homolog 2 (EZH2), the target gene of let-7b-5p in NSCLC. Moreover, EZH2 transcriptionally induced the expression of PKMYT1 to activate the Wnt/ß-catenin pathway. Sh-EZH2 and sh-PKMYT1 neutralized the supporting effects of KDM2B on cell proliferation, invasion and migration. Additionally, deletion of KDM2B reduced the xenograft volumes in nude mice. In conclusion, KDM2B induces the EZH2/PKMYT1/Wnt/ß-catenin axis by inhibiting the let-7b-5p expression, which promotes NSCLC growth. More investigations are essential to determine the oncogenic role of KDM2B in NSCLC.

High PLA2 level is correlated with glioblastoma progression via regulating DNA replication.

Phospholipases A2 (PLA2) are a superfamily of enzymes, playing a critical role in the development of various human cancers. However, the mechanism of PLA2 as an oncogene in glioblastoma remains largely unknown. In this study, we explored the effects of PLA2 on glioblastoma and investigated the underlying mechanism. The results showed that PLA2 was highly expressed in glioblastoma. Patients with a high PLA2 level have low overall survival than those with low PLA2 expression. PLA2 overexpression promoted glioblastoma cell proliferation and viability and inhibited cell apoptosis by inducing cell cycle transition from G1 to S stage. Knockdown of PLA2 inhibited tumor growth in the xenograft mice model. In addition, PLA2 knockdown decreased the protein level of MCM2 and MCM5. These findings identify PLA2 as an oncogene in glioblastoma progression and provide a promising strategy to treat glioblastoma in the future.