Suppression of PI3K/Akt/mTOR/c-Myc/mtp53 Positive Feedback Loop Induces Cell Cycle Arrest by Dual PI3K/mTOR Inhibitor PQR309 in Endometrial Cancer Cell Lines

Hsin, I.; Shen, Huang‐Pin; Chang, Haṡok; Wang, Po-Hui

doi:10.3390/cells10112916

Cited by 24 publications

(20 citation statements)

References 45 publications

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“…A previous study found that the activation of PI3K-Akt and P53 signaling pathways had a very high risk of EC progression. [ 21 ] In the Rap1 signaling pathway, Rap1GAP can act as a tumor suppressor inhibiting the Ras superfamily protein Rap1 in EC, and it is an independent prognostic factor in EC. [ 22 ] EGFR tyrosine kinase inhibitor is a small molecule EGFR inhibitor that can inhibit tyrosine kinase activation, block the EGFR signaling pathway, inhibit the proliferation and metastasis of tumor cells, and promote apoptosis through competitive endogenous ligand binding to EFGR.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic analysis of differentially expressed profiles of lncRNAs and miRNAs with their related ceRNA network in endometrial cancer

Zhou

et al. 2023

Medicine

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Increasing evidence suggests that long non-coding riboneucleic acids (lncRNAs), as competing endogenous RNA (ceRNA), play a key role in the initiation, invasion, and metastasis of cancer. As a new hypothesis, the lncRNA-micro RNA (miRNA)-messenger RNA (mRNA), ceRNA regulatory network has been successfully constructed in a variety of cancers. However, lncRNA, which plays a ceRNA function in endometrial cancer (EC), is still poorly understood. In this study, we downloaded EC expression profiling from The Cancer Genome Atlas database and used the R software "edgeR" package to analyze the differentially expressed genes between EC and normal endometrium samples. Then, differentially expressed (DE) lncRNAs, miRNAs and mRNAs were selected to construct a lncRNA-miRNA-mRNA prognosis-related regulatory network based on interaction information. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed on the genes in the network to predict the potential underlying mechanisms and functions of lncRNAs in EC. Kaplan-Meier method and the log-rank test were used for survival analysis. Based on the "ceRNA hypothesis," we constructed a co-expression network of mRNA and lncRNA genes mediated by miRNA in the process of tumor genesis. Furthermore, we successfully constructed a dysregulated lncRNA-associated ceRNA network containing 96 DElncRNAs, 27 DEmiRNAs, and 74 DEmRNAs. Through Kaplan-Meier curve analysis, we found that 9 lncRNAs, 3 miRNAs, and 12 mRNAs were significantly correlated with the overall survival rate of patients among all lncRNAs, miRNAs, and mRNAs involved in ceRNA (P < .05). Our research provides a new perspective for the interaction among lncRNAs, miRNAs, and mRNA and lays the foundation for further research on the mechanism of lncRNAs in the occurrence of EC.Abbreviations: DE = differentially expressed, ceRNA = competing endogenous RNAs, DEGs = differentially expressed genes, EC = endometrial cancer, GO = gene ontology, KEGG = Kyoto Encyclopedia of Genes and Genomes, lncRNA = long noncoding RNA, mRNA = messenger RNA, miRNA = micro RNA, OS = overall survival, RNA = ribonucleic acid, TCGA = The Cancer Genome Atlas.

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Section: Discussionmentioning

confidence: 99%

Bioinformatic analysis of differentially expressed profiles of lncRNAs and miRNAs with their related ceRNA network in endometrial cancer

Zhou

et al. 2023

Medicine

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“…S6K2 inhibitor induces G1 arrest to inhibit the proliferation of melanoma cells [ 291 ]. PI3K/mTOR inhibitor PQR309 inhibits the PI3K/AKT/mTOR/c-Myc axis and causes G1 arrest of endometrial cancer cells [ 265 ]. Mature SREBP1 is regulated by hyperphosphorylation for G2/M arrested cervical cancer cells [ 301 ].…”

Section: Akt Effectors Modulate Cell Functionsmentioning

confidence: 99%

The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products

et al. 2022

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Oxidative stress and AKT serine-threonine kinase (AKT) are responsible for regulating several cell functions of cancer cells. Several natural products modulate both oxidative stress and AKT for anticancer effects. However, the impact of natural product-modulating oxidative stress and AKT on cell functions lacks systemic understanding. Notably, the contribution of regulating cell functions by AKT downstream effectors is not yet well integrated. This review explores the role of oxidative stress and AKT pathway (AKT/AKT effectors) on ten cell functions, including apoptosis, autophagy, endoplasmic reticulum stress, mitochondrial morphogenesis, ferroptosis, necroptosis, DNA damage response, senescence, migration, and cell-cycle progression. The impact of oxidative stress and AKT are connected to these cell functions through cell function mediators. Moreover, the AKT effectors related to cell functions are integrated. Based on this rationale, natural products with the modulating abilities for oxidative stress and AKT pathway exhibit the potential to regulate these cell functions, but some were rarely reported, particularly for AKT effectors. This review sheds light on understanding the roles of oxidative stress and AKT pathway in regulating cell functions, providing future directions for natural products in cancer treatment.

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“…The PI3K/AKT/mTOR pathway can inhibit autophagy [14]. In addition, FAM83D contributed to the progression of several cancers via this pathway [13,14]. Previous studies confirmed FAM83D had effects on the PI3K/AKT/mTOR axis, which could further affect multiple cellular processes in cancer progression, such as proliferation, apoptosis, and autophagy [12,15].…”

Section: Introductionmentioning

confidence: 98%

“…Activation of phosphoinositol 3-kinase (PI3K) or mTOR is the most common event in the development of human cancers, including EC [12]. The alteration of PI3K/AKT/mTOR pathway is related to the pathogenesis of endometrial carcinoma [13]. The PI3K/AKT/mTOR pathway can inhibit autophagy [14].…”

Section: Introductionmentioning

confidence: 99%

Knockdown of FAM83D inhibits endometrial cancer cell viability and induces autophagy via the PI3K/AKT/mTOR axis

2022

European Journal of Gynaecological Oncology

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It is important to search new diagnostic and prognostic markers of endometrial cancer (EC) and uncover the possible mechanisms. Family with sequence similarity 83 member D (FAM83D) is proved to have carcinogenic properties and act as a new oncogene. FAM83D is overexpressed in endometrial cancer, but the role of FAM83D in EC is still unclear. Here the role of FAM83D was investigated in EC progression. FAM83D depletion inhibited the proliferation of EC cells. The knockdown of FAM83D induced EC cell cycle arrest. Moreover, its depletion stimulated the apoptosis and autophagy of EC cells. We further found FAM83D depletion inhibited progression of EC via targeting phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) axis. We therefore thought FAM83D could serve as a EC target.

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Suppression of PI3K/Akt/mTOR/c-Myc/mtp53 Positive Feedback Loop Induces Cell Cycle Arrest by Dual PI3K/mTOR Inhibitor PQR309 in Endometrial Cancer Cell Lines

Cited by 24 publications

References 45 publications

Bioinformatic analysis of differentially expressed profiles of lncRNAs and miRNAs with their related ceRNA network in endometrial cancer

Bioinformatic analysis of differentially expressed profiles of lncRNAs and miRNAs with their related ceRNA network in endometrial cancer

The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products

Knockdown of FAM83D inhibits endometrial cancer cell viability and induces autophagy via the PI3K/AKT/mTOR axis

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