Emerging role of PI3K/AKT in tumor-related epigenetic regulation

Yang, Qi; Jiang, Wei; Hou, Peng

doi:10.1016/j.semcancer.2019.04.001

Cited by 148 publications

(95 citation statements)

References 193 publications

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“…Extracellular stimulus signals are dependent on inositol lipid signaling molecules, which are transported to the nucleus through cell membrane transformation, whereas PI3K is an important cellular signal transduction molecule. 41 Previous cancer studies have found that fucoidan can inhibit the PI3K/Akt signaling pathway, which has been further confirmed in OC cells. 7,31,32 The results of the present study showed that PI3K gene transcription and protein expression were inhibited by fucoidan via Akt phosphorylation.…”

Section: Discussionmentioning

confidence: 68%

<p>The Natural Product Fucoidan Inhibits Proliferation and Induces Apoptosis of Human Ovarian Cancer Cells: Focus on the PI3K/Akt Signaling Pathway</p>

Liu

Yang

Peng

et al. 2020

CMAR

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Objective: Ovarian cancer (OC) is the leading cause of death among gynecological tumors; however, no effective treatment is currently available. Fucoidan, which is extracted from marine algae, has significant anti-cancer effects. The aim of this study was to determine the effects of fucoidan on the proliferation and apoptosis of OC cells through inhibition of the PI3K/Akt signaling pathway. Methods: Human ovarian normal epithelial cells (IOSE80) and human OC cells (SKOV-3, A2780, OVCAR-3, TOV-112D, and Caov-3) were selected to verify the safety of fucoidan at various doses in SKOV-3 and Caov-3 cells as well as a xenograft mouse model using various molecular biology techniques. Results: Fucoidan had no significant effect on normal ovarian epithelial cells, but had significantly inhibited the proliferation of OC cells, induced cell cycle arrest at the G0/G1 phase, increased the proportion of apoptotic cells and expression of pro-apoptotic proteins, and inhibited the expression of PI3K and phosphorylation of Akt, which could be partly rescued by IGF-1. Conclusion: Fucoidan had anti-tumor effects both in vivo and in vitro via a mechanism that is related to the inhibition of the PI3K/Akt signaling pathway.

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Section: Discussionmentioning

confidence: 68%

<p>The Natural Product Fucoidan Inhibits Proliferation and Induces Apoptosis of Human Ovarian Cancer Cells: Focus on the PI3K/Akt Signaling Pathway</p>

Liu

Yang

Peng

et al. 2020

CMAR

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“…The PI3K/Akt signaling pathway functions as a vital intermediary to facilitate various cellular and physiological processes, including the cell cycle, cellular growth, differentiation, survival, apoptosis, metabolism, angiogenesis, and migration [26]. Accumulating evidence has displayed that crucial epigenetic modifiers are directly or indirectly regulated by PI3K/AKT signaling and involved in oncogenesis of PI3K cascade in cancers [27]. The core of p53 signaling pathway is p53, which functions as safeguarding the integrity of the genome.…”

Section: Discussionmentioning

confidence: 99%

Identification of Potentially Functional CircRNA-miRNA-mRNA Regulatory Network in Gastric Carcinoma using Bioinformatics Analysis

2019

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Departmental sources Background: As all we know, gastric cancer (GC) is a highly aggressive disease. Recently, circular RNA (circRNA) was found to play a vital role in regulation of GC. Some circRNAs could regulate messenger RNA (mRNA) expression by functioning as a microRNA (miRNA) sponge. Nevertheless, the circRNA-miRNA-mRNA regulatory network involved GC rarely has been explored and researched. Material/Methods: All the differentially expressed circRNAs, miRNAs, and mRNA were derived from Gene Expression Omnibus (GEO) microarray data (GSE78092, GSE89143, GSE93415, and GSE54129). GC level 3 miRNA-sequencing data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Furthermore, a circRNA-miRNA-mRNA regulatory network was constructed by Cytoscape (version 3.6.1). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway revealed the functions and signaling pathways associated with these target genes. Hub genes of protein-protein interaction (PPI) network were identified by STRING database and cytoHubba. Results: The regulatory network consists of 3 circRNAs, 22 miRNAs, and 128 mRNAs. Only 3 miRNAs of the network were consistent with the expression of TCGA and were associated with some clinical features. The results of the functional analysis of 128 mRNAs showed that GO analysis and KEGG pathways of inclusion criteria were 49 and 24, respectively. PPI network and Cytoscape showed that the top 10 hub genes were MYC, CTGF, TGFBR2, TGFBR1, SERPINE1, KRAS, ZEB1, THBS1, CDK6, and TNS1; 4 of which were verified by GEPIA based on TCGA. Highly expressed SERPINE1 had a poor OS (over survival) and DFS (disease-free survival), and TGFBR1 expression increased along with the increase of clinical stages. Conclusions: This study looked at a circRNA-miRNA-mRNA regulatory network associated with GC and explored the potential functions of mRNA in the network, then identified a new molecular marker for prediction, prognosis, and therapeutic targets for clinical patients.

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“…Epigenetic modifiers participate in the PI3K/Akt/mTOR pathway, contributing to the oncogenicity of PI3K in cancer. The cooperation of the PI3K/Akt/mTOR pathway with epigenetic reprogramming involves modulation of DNA methylation and histone methylation to promote transcriptional competence [254,255]. Because of this collaboration, combination strategies with PI3K/Akt/mTOR inhibitors and epigenetic therapies have been exploited.…”

Section: Pi3k/akt/mtor Inhibitors In Combination With Epigenetic Targmentioning

confidence: 99%

Targeting PI3K/Akt/mTOR in AML: Rationale and Clinical Evidence

Darici

Alkhaldi

Horne

et al. 2020

JCM

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Acute myeloid leukemia (AML) is a highly heterogeneous hematopoietic malignancy characterized by excessive proliferation and accumulation of immature myeloid blasts in the bone marrow. AML has a very poor 5-year survival rate of just 16% in the UK; hence, more efficacious, tolerable, and targeted therapy is required. Persistent leukemia stem cell (LSC) populations underlie patient relapse and development of resistance to therapy. Identification of critical oncogenic signaling pathways in AML LSC may provide new avenues for novel therapeutic strategies. The phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) signaling pathway, is often hyperactivated in AML, required to sustain the oncogenic potential of LSCs. Growing evidence suggests that targeting key components of this pathway may represent an effective treatment to kill AML LSCs. Despite this, accruing significant body of scientific knowledge, PI3K/Akt/mTOR inhibitors have not translated into clinical practice. In this article, we review the laboratory-based evidence of the critical role of PI3K/Akt/mTOR pathway in AML, and outcomes from current clinical studies using PI3K/Akt/mTOR inhibitors. Based on these results, we discuss the putative mechanisms of resistance to PI3K/Akt/mTOR inhibition, offering rationale for potential candidate combination therapies incorporating PI3K/Akt/mTOR inhibitors for precision medicine in AML.

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Emerging role of PI3K/AKT in tumor-related epigenetic regulation

Cited by 148 publications

References 193 publications

<p>The Natural Product Fucoidan Inhibits Proliferation and Induces Apoptosis of Human Ovarian Cancer Cells: Focus on the PI3K/Akt Signaling Pathway</p>

<p>The Natural Product Fucoidan Inhibits Proliferation and Induces Apoptosis of Human Ovarian Cancer Cells: Focus on the PI3K/Akt Signaling Pathway</p>

Identification of Potentially Functional CircRNA-miRNA-mRNA Regulatory Network in Gastric Carcinoma using Bioinformatics Analysis

Targeting PI3K/Akt/mTOR in AML: Rationale and Clinical Evidence

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