The PI3K/Akt/mTOR pathway in lung cancer; oncogenic alterations, therapeutic opportunities, challenges, and a glance at the application of nanoparticles

Sanaei, Mohammad‐Javad; Razi, Sara; Pourbagheri‐Sigaroodi, Atieh; Bashash, Davood

doi:10.1016/j.tranon.2022.101364

Cited by 83 publications

(46 citation statements)

References 162 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, GG genotype of +405 G/C VEGFA polymorphism is associated with a lower risk for infantile hemangioma ( 15 ). The PI3K/AKT pathway has been shown to regulate various biological processes, including cell survival, mobility and malignant transformation ( 16 , 17 ). In particular, this signaling pathway has been reported to be associated with the pathogenesis and progression of hemangioma ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑203a‑3p suppresses endothelial cell proliferation and invasion, and promotes apoptosis in hemangioma by inactivating the VEGF‑mediated PI3K/AKT pathway

Zhuo

et al. 2022

Exp Ther Med

View full text Add to dashboard Cite

Our previous study demonstrated that was involved in the regulation of long non-coding RNA MEG8-mediated the progression of hemangioma, which is a benign tumor characterized by endothelial hyperplasia in the blood vessels and primarily occurring in infants and females. Therefore, the present study aimed to further investigate the effects of miR-203a-3p on endothelial cell proliferation, invasion and apoptosis, as well as its underlying mechanism in hemangioma. Human hemangioma endothelial cells (HemECs) were first transfected with either miR-203a-3p mimics or a miR-203a-3p inhibitor. Subsequently, vascular endothelial growth factor A (VEGFA) was overexpressed in these cells. Cell proliferation (by Cell Counting Kit-8 assay), apoptosis (by TUNEL assay), invasion (by Transwell assay) and PI3K/AKT signaling (by western blot) were assessed following transfection of these cells. Notably, transfection with miR-203a-3p mimics caused a reduction in cell proliferation, invasion and in the phosphorylation levels of PI3K and AKT, and promoted cell apoptosis in HemECs. By contrast, transfection with the miR-203a-3p inhibitor exerted the opposite effects compared with those of the miR-203a-3p mimics. miR-203a-3p was revealed to directly suppress VEGFA expression in HemECs. VEGFA overexpression alone increased cell proliferation and invasion, but decreased apoptosis. Furthermore, VEGFA co-transfection reversed the effects mediated by miR-203a-3p mimics transfection in HemECs. Mechanistically, miR-203a-3p was demonstrated to inactivate the PI3K/AKT pathway, whereas VEGFA overexpression produced the opposite effect. VEGFA co-transfection also attenuated the miR-203a-3p mimics-induced inactivation of PI3K/AKT signaling in HemECs. In conclusion, these data suggested that miR-203a-3p may inhibit endothelial cell proliferation and invasion, and promote apoptosis by inactivating VEGFA and PI3K/AKT signaling in hemangioma. These findings also implicated miR-203 as a possible treatment option for this disease.

show abstract

Section: Introductionmentioning

confidence: 99%

MicroRNA‑203a‑3p suppresses endothelial cell proliferation and invasion, and promotes apoptosis in hemangioma by inactivating the VEGF‑mediated PI3K/AKT pathway

Zhuo

et al. 2022

Exp Ther Med

View full text Add to dashboard Cite

show abstract

“…The PI3K/AKT/mTOR pathway plays a crucial role in diverse biological behaviors including cell growth, migration, metabolism, and death ( 41 ). In LUAD, the aberrant activation in this signaling has been indicated to induce uncontrolled growth, drug resistance, sustained angiogenesis, as well as distant metastasis ( 42 ). P53 protein is a transcription factor known as the “guardian gene” because of its significant role in preserving genomic integrity.…”

Section: Discussionmentioning

confidence: 99%

Integrated single-cell and transcriptome sequencing analyses determines a chromatin regulator-based signature for evaluating prognosis in lung adenocarcinoma

et al. 2022

View full text Add to dashboard Cite

BackgroundAccumulating evidence has highlighted the significance of chromatin regulator (CR) in pathogenesis and progression of cancer. However, the prognostic role of CRs in LUAD remains obscure. We aim to detect the prognostic value of CRs in LUAD and create favorable signature for assessing prognosis and clinical value of LUAD patients.MethodsThe mRNA sequencing data and clinical information were obtained from TCGA and GEO databases. Gene consensus clustering analysis was utilized to determine the molecular subtype of LUAD. Cox regression methods were employed to set up the CRs-based signature (CRBS) for evaluating survival rate in LUAD. Biological function and signaling pathways were identified by KEGG and GSEA analyses. In addition, we calculated the infiltration level of immunocyte by CIBERSORT algorithm. The expressions of model hub genes were detected in LUAD cell lines by real-time polymerase chain reaction (PCR).ResultsKEGG analysis suggested the CRs were mainly involved in histone modification, nuclear division and DNA modification. Consensus clustering analysis identified a novel CRs-associated subtype which divided the combined LUAD cohort into two clusters (C1 = 217 and C2 = 296). We noticed that a remarkable discrepancy in survival rate among two clusters. Then, a total of 120 differentially expressed CRs were enrolled into stepwise Cox analyses. Four hub CRs (CBX7, HMGA2, NPAS2 and PRC1) were selected to create a risk signature which could accurately forecast patient outcomes and differentiate patient risk. GSEA unearthed that mTORC1 pathway, PI3K/Akt/mTOR and p53 pathway were greatly enriched in CRBS-high cohort. Moreover, the infiltration percentages of macrophage M0, macrophage M2, resting NK cells, memory B cells, dendritic cells and mast cells were statistically significantly different in the two groups. PCR assay confirmed the differential expression of four model biomarkers.ConclusionsAltogether, our project developed a robust risk signature based on CRs and offered novel insights into individualized treatment for LUAD cases.

show abstract

“…Notably, the new wave of studies has uncovered the role played by the PI3K/Akt pathway not only in lung cancer cell survival but also at the crossroads of different cancer-related pathways. [25]. The oncogenic role of MAPK, RAS, and EGFR deregulation has been also highlighted in the development of NSCLC [26];…”

Section: Discussionmentioning

confidence: 99%

Identification of an immune-related genes signature in lung adenocarcinoma to predict survival and response to immune checkpoint inhibitors

Davoodi-Moghaddam

Jafari-Raddani

Kordasti

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Background Although advances in immune checkpoint inhibitor (ICI) research have provided a new treatment approach for lung adenocarcinoma (LUAD) patients, their survival is still unsatisfactory, and there are issues in the era of response prediction to immunotherapy. We aimed to develop a prognostic model based on immune-related genes (IRGs) to predict the overall survival (OS) as well as response to ICIs in LUAD patients. Methods Using bioinformatics methods, a prognostic signature was constructed and its predictive ability was validated both in the internal and external datasets (GSE68465). We also explored the tumor-infiltrating immune cells, mutation profiles, and immunophenoscore (IPS) in the low-and high-risk groups. Results A prognostic signature based on 9-IRGs, including BIRC5, CBLC, S100P, SHC3, ANOS1, VIPR1, LGR4, PGC, and IGKV4.1 was developed. According to multivariate analysis, the 9-IRG signature provided an independent prognostic factor for OS in LUAD patients. The low-risk group had better OS, and the tumor mutation burden (TMB) was significantly lower in this group. Moreover, the risk scores were negatively associated with the tumor-infiltrating immune cells, like CD8+ T cells, macrophages, dendritic cells, and NK cells. In addition, the IPS were significantly higher in the low-risk group as they had higher gene expression of immune checkpoints, suggesting that ICIs could be a promising treatment option for low-risk LUAD patients. Conclusion Our 9-IRGs prognostic signature could be useful in predicting the survival of LUAD patients and their response to ICIs; hoping this model paves the way for better stratification and management of patients in clinical practice.

show abstract

The PI3K/Akt/mTOR pathway in lung cancer; oncogenic alterations, therapeutic opportunities, challenges, and a glance at the application of nanoparticles

Cited by 83 publications

References 162 publications

MicroRNA‑203a‑3p suppresses endothelial cell proliferation and invasion, and promotes apoptosis in hemangioma by inactivating the VEGF‑mediated PI3K/AKT pathway

MicroRNA‑203a‑3p suppresses endothelial cell proliferation and invasion, and promotes apoptosis in hemangioma by inactivating the VEGF‑mediated PI3K/AKT pathway

Integrated single-cell and transcriptome sequencing analyses determines a chromatin regulator-based signature for evaluating prognosis in lung adenocarcinoma

Identification of an immune-related genes signature in lung adenocarcinoma to predict survival and response to immune checkpoint inhibitors

Contact Info

Product

Resources

About