TY  - JOUR
T1  - Regulation of Lung Adenocarcinoma Metastasis by AH-6809 via NLRP7 and Prognostic Evaluation of Critical Metastasis-Associated Genes
A1  - Khalid Rahman
A1  - Ayesha Malik
A1  - Farhan Iqbal
A1  - Usman Tariq
JF  - Specialty Journal of Pharmacognosy, Phytochemistry, and Biotechnology
JO  - Spec J Pharmacogn Phytochem Biotechnol
SN  - 3062-441X
Y1  - 2023
VL  - 3
IS  - 1
DO  - 10.51847/6epWrws46C
SP  - 142
EP  - 163
N2  - Lung adenocarcinoma (LUAD) ranks among the deadliest cancers worldwide, with metastasis representing the primary cause of mortality. Despite advancements in diagnosis and treatment, the processes enabling LUAD cells to infiltrate the blood-brain barrier remain largely unknown. Although genomic profiling has provided insight into primary tumors, the genetic determinants and clinical significance of metastasis in LUAD are still poorly characterized. This study aims to delineate genomic differences between LUAD tumors that metastasize to the brain and those that do not, identify potential prognostic biomarkers, and investigate the modulatory effects of AH-6809 on molecular pathways governing metastasis, particularly focusing on post-translational modifications (PTMs). Data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) were analyzed to detect differentially expressed genes (DEGs) between brain-metastatic and non-metastatic LUAD samples. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to identify critical gene modules, and their prognostic value was assessed via Kaplan-Meier survival analysis. In vitro experiments, including CCK8 proliferation assays and qRT-PCR, were conducted to evaluate the anti-tumor effects of AH-6809, while immunofluorescence assays measured apoptosis and inflammation-related markers. Analysis revealed distinct genomic profiles between brain-metastatic and non-metastatic LUAD, identifying NLRP7, FIBCD1, and ELF5 as significant prognostic indicators. Treatment with AH-6809 suppressed LUAD cell proliferation, induced apoptosis, and altered epithelial-mesenchymal transition (EMT) marker expression. Knockdown of NLRP7 diminished these effects, highlighting its critical role in metastasis regulation. Supporting evidence from the literature demonstrated that AH-6809 exerts tumor-suppressive effects, particularly in NLRP7-deficient cells, by inhibiting growth and promoting apoptosis. AH-6809 also modulated SUMO1-dependent PTMs and reduced expression of EMT markers such as VIM and CDH2, with partial reversal observed upon NLRP7 silencing. Immunofluorescence further confirmed enhanced apoptosis and inflammatory responses in LUAD cells treated with AH-6809, especially under NLRP7 knockdown conditions. These regulatory effects appear to involve SUMO1-mediated PTMs and NQO1, warranting further investigation to fully understand the mechanisms and therapeutic potential. The findings underscore the importance of NLRP7 and associated genes in LUAD metastasis and suggest that AH-6809 represents a promising candidate for targeted therapy against brain-metastatic LUAD.
UR  - https://galaxypub.co/article/regulation-of-lung-adenocarcinoma-metastasis-by-ah-6809-via-nlrp7-and-prognostic-evaluation-of-criti-bhpjcsik2q2nd4p
ER  -