ABSTRACT
SUMMARY: We investigated Tweety Family Member 3 (TTYH3) level in lung adenocarcinoma (LUAD) and its relationship with immune infiltration in tumors by bioinformatics. Differential expressions of TTYH3 in lung cancer were analyzed with Oncomine, TIMER, GEO, UALCAN and HPA. Relationship of TTYH3 mRNA/protein levels with clinical parameters was analyzed by UALCAN. Co-expressed genes of TTYH3 in LUAD were analyzed using Cbioportal. Its relationship with LUAD prognosis was analyzed by Kaplan-Meier plotter. GO and KEGG analysis were performed. Correlation between TTYH3 and tumor immune infiltration were tested by TIMER, TISIDB and GEPIA. We found that TTYH3 was significantly increased in LUAD tissues. TTYH3 high expression was closely related to poor overall survival, post progression survival and first progression in LUAD patients. TTYH3 mRNA/protein levels were significantly associated with multiple pathways. Specifically, TTYH3 up-regulation was mostly related to biological regulation, metabolic process, protein blinding, extracellular matrix organization and pathways in cancer. Moreover, TTYH3 was positively associated with immune cell infiltration in LUAD. Finally, TTYH3 was highly expressed in LUAD as revealed by meta-analysis. TTYH3 is closely related to the prognosis of LUAD and immune cell infiltration, and it can be used as a prognostic biomarker for LUAD and immune infiltration.
Investigamos por bioinformática el nivel de Tweety Family Member 3 (TTYH3) con adenocarcinoma de pulmón (LUAD) y su relación con la infiltración inmune en tumores. Las expresiones diferenciales de TTYH3 en cáncer de pulmón se analizaron con Oncomine, TIMER, GEO, UALCAN y HPA. Con UALCAN se analizó la relación de los niveles de ARNm/proteína de TTYH3 con los parámetros clínicos. Los genes coexpresados de TTYH3 en LUAD se analizaron utilizando Cbioportal. Su relación con el pronóstico LUAD se analizó mediante plotter de Kaplan- Meier. Se realizaron análisis GO y KEGG. TIMER, TISIDB y GEPIA probaron la correlación entre TTYH3 y la infiltración inmune tumoral. Encontramos que TTYH3 aumentó significativamente en los tejidos LUAD. La alta expresión de TTYH3 estuvo estrechamente relacionada con una supervivencia general deficiente, supervivencia posterior a la progresión y primera progresión en pacientes con LUAD. Los niveles de ARNm/ proteína de TTYH3 se asociaron significativamente con múltiples vías. Específicamente, la regulación positiva de TTYH3 se relacionó principalmente con la regulación biológica, el proceso metabólico, el cegamiento de proteínas, la organización de la matriz extracelular y las vías en el cáncer. Además, TTYH3 se asoció positivamente con la infiltración de células inmunitarias en LUAD. Finalmente, TTYH3 se expresó altamente en LUAD como lo reveló el metanálisis. TTYH3 está estrechamente relacionado con el pronóstico de LUAD y la infiltración de células inmunitarias, y se puede utilizar como biomarcador pronóstico para LUAD y la infiltración de células inmunitarias.
Subject(s)
Humans , Chloride Channels/metabolism , Adenocarcinoma of Lung/diagnosis , Lung Neoplasms/diagnosis , Prognosis , RNA, Messenger , Lymphocytes , Biomarkers, Tumor , Chloride Channels/genetics , Adenocarcinoma of Lung/immunology , Adenocarcinoma of Lung/metabolism , Lung Neoplasms/immunology , Lung Neoplasms/metabolismABSTRACT
OBJECTIVE@#Although there have been improvements in targeted therapy and immunotherapy, the majority of lung adenocarcinoma (LUAD) patients still lack effective therapies. Consequently, it is urgent to screen for new diagnosis biomarkers and pharmacological targets. Junctional adhesion molecule-like protein (JAML) was considered to be an oncogenic protein and may be a novel therapeutic target in LUAD. Kaempferol is a natural flavonoid that exhibits antitumor activities in LUAD. However, the effect of kaempferol on JAML is still unknown.@*METHODS@#Small interfering RNA was used to knockdown JAML expression. The cell viability was determined using the cell counting kit-8 assay. The proliferation of LUAD cells was evaluated using the 5-ethynyl-2'-deoxyuridine incorporation assay. The migration and invasion of LUAD cells were evaluated by transwell assays. Molecular mechanisms were explored by Western blotting.@*RESULTS@#JAML knockdown suppressed proliferation, migration and invasion of LUAD cells, and JAML deficiency restrained epithelial-mesenchymal transition (EMT) via inactivating the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Using a PI3K activator (740Y-P), rescue experiments showed that phenotypes to JAML knockdown in LUAD cells were dependent on the PI3K/AKT/mTOR pathway. Kaempferol also inhibited proliferation, migration and invasion of A549 and H1299 cells and partially suppressed EMT through the PI3K/AKT/mTOR pathway. Knockdown of JAML ameliorated the inhibitory effect of kaempferol on LUAD cells. Kaempferol exerted anticancer effects by targeting JAML.@*CONCLUSION@#JAML is a novel target for kaempferol against LUAD cells. Please cite this article as: Wu Q, Wang YB, Che XW, Wang H, Wang W. Junctional adhesion molecule-like protein as a novel target for kaempferol to ameliorate lung adenocarcinoma. J Integr Med. 2023; 21(3): 268-276.