E2F2 inhibition induces autophagy via the PI3K/Akt/mTOR pathway in gastric cancer

Li, Hui; Zhao, Shufen; Shen, Lianju; Wang, Peige; Liu, Shihai; Ma, Yuanyuan; Liang, Zhiwei; Wang, Gongjun; Lv, Jing; Qiu, Wensheng

doi:10.18632/aging.202891

Cited by 23 publications

(21 citation statements)

References 45 publications

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“…34 E2F2 was highly expressed in both gastric cancer tissues and cells compared with normal gastric tissues/cells, which promoted the migration and invasiveness of gastric cancer cells. 35 It was also reported that the over-expressed miR-490-5p could inhibit the metastasis of hepatocellular carcinoma cells by down-regulating E2F2 expression levels. 36 In our research, no significant differences were seen in the expression of E2F2 between normal tissues and carcinoma tissues in patients.…”

Section: Discussionmentioning

confidence: 98%

Identification of the Expression and Clinical Significance of E2F Family in Clear Cell Renal Cell Carcinoma

Chen¹,

Zhang²,

Hu³

et al. 2022

IJGM

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Background: Multiple studies have identified that E2F transcriptions act as important regulators for the tumorigenesis and progression of several human cancers. However, little is known about the function of E2Fs in clear cell renal cell carcinoma (ccRCC). Methods: We firstly investigated the expression levels, genetic alteration, and biological function of E2Fs in patients with ccRCC and the connections between the immune cell infiltration and the overall survivals of ccRCC patients with the E2Fs expression levels based on UALCAN, The Cancer Genome Atlas database, Gene Expression Profiling Interactive Analysis, TIMER, STRING, GSCALite and cBioPortal databases. Results: Results revealed that the expression levels of E2F1/2/3/4/6/7/8 were markedly upregulated in patients with ccRCC, while the expression of E2F5 displayed an opposite trend. We also experimentally validated the overexpression of E2F3/4/7 in human ccRCC tissues and ccRCC cell lines. Furthermore, the high E2F1/2/3/4/7/8 expression levels were clearly associated with worse pathological characteristics of ccRCC, including high pathological stage, poor molecular subtypes and high tumor grade. Meanwhile, high expression levels of E2F1/2/4/7/8 were evidently associated with worse overall survivals (OSs) and progression-free survivals (PFSs) of patients harboring ccRCC. Univariate and multivariate analyses illustrated that the expressions of E2F4/5/7 were independent factors associated with the OSs and PFSs of patients with ccRCC. Meanwhile, the mutations in E2Fs were also significantly related to poor OSs and PFSs of patients with ccRCC. Mechanically, the E2Fs genes synergistically promoted the progression of ccRCC by accelerating the cell cycle and inhibiting DNA damage response and apoptosis after performing the protein structure, functional enrichment, and PPI network analyses. In addition, E2Fs genes were also significantly associated with tumor immune cells infiltration and the drug sensitivity in ccRCC. Conclusion:As a result, E2F4/7 were highly expressed in ccRCC and significantly associated with worse pathological characteristics of ccRCC, including high pathological stage, poor molecular subtypes and high tumor grade, tumor immune cell infiltration, and drug sensitivity, consequently translating into poor OSs and PFSs of patients with ccRCC. Our results indicated that E2F4/7 could be potential biomarkers and therapeutic targets of ccRCC patients.

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Section: Discussionmentioning

confidence: 98%

Identification of the Expression and Clinical Significance of E2F Family in Clear Cell Renal Cell Carcinoma

Chen¹,

Zhang²,

Hu³

et al. 2022

IJGM

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“…MYC is a core of the oncogenic process (29) and can promote tumorigenesis with its regulation of transcription (30). E2F plays a crucial role in the CDK- RB-E2F axis, the core transcriptional machinery to drive cell cycle progression (31). E2F2, a member of the E2F family, is a regulator in PI3K/Akt/mTOR pathway, which is strongly associated with autophagy for it inhibits autophagy in GC cells when overexpressed (31).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of autophagy-related clusters and individual risk model for immunotherapy response prediction in gastric cancer

Yao

Hu²,

Ma³

et al. 2023

Front. Oncol.

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IntroductionAutophagy can be triggered by oxidative stress and is a double-edged sword involved in the progression of multiple malignancies. However, the precise roles of autophagy on immune response in gastric cancer (GC) remain clarified.MethodsWe endeavor to explore the novel autophagy-related clusters and develop a multi-gene signature for predicting the prognosis and the response to immunotherapy in GC. A total of 1505 patients from eight GC cohorts were categorized into two subtypes using consensus clustering. We compare the differences between clusters by the multi-omics approach. Cox and LASSO regression models were used to construct the prognostic signature.ResultsTwo distinct clusters were identified. Compared with cluster 2, the patients in cluster 1 have favorable survival outcomes and lower scores for epithelial-mesenchymal transition (EMT). The two subtypes are further characterized by high heterogeneity concerning immune cell infiltration, somatic mutation pattern, and pathway activity by gene set enrichment analysis (GSEA). We obtained 21 autophagy-related differential expression genes (DEGs), in which PTK6 amplification and BCL2/CDKN2A deletion were highly prevalent. The four-gene (PEA15, HSPB8, BNIP3, and GABARAPL1) risk signature was further constructed with good predictive performance and validated in 3 independent datasets including our local Tianjin cohort. The risk score was proved to be independent prognostic factor. A prognostic nomogram showed robust validity of GC survival. The risk score was significantly associated with immune cell infiltration status, tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoint molecules. Furthermore, the model was efficient for predicting the response to tumor-targeted agent and immunotherapy and verified by the IMvigor210 cohort. This model is also capable of discriminating between low and high-risk patients receiving chemotherapy.ConclusionAltogether, our exploratory research on the landscape of autophagy-related patterns may shed light on individualized therapies and prognosis in GC.

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“…find that E2F2 accelerates autophagy in gastric cancer via modulating the PI3K/Akt/mammalian target of rapamycin (mTOR) pathway [ 28 ]. The latest study has elucidated that E2F2 drives glioma’s progression via the PI3K/Akt pathway in a 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4)-dependent manner [ 29 ]. The results of the study further affirmed the vital role of E2F2 in modulating PI3K/Akt signal.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-631 deriving from bone marrow mesenchymal stem cell exosomes facilitates the malignant behavior of non-small cell lung cancer via modulating the E2F family of transcription factor 2/phosphatidylinositol 3‐kinase/Akt signaling pathway

Hong¹,

Yu²,

Zhang³

et al. 2022

Bioengineered

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The exosomes (Exo) had always been considered as transport vectors for microRNA (miRNA). An increasing number of data had clarified the influence of Exo on the cell progression of non-small cell lung cancer (NSCLC). Nevertheless, its specific mechanism had not yet been verified. This work was to explore the potential mechanism of Exo-derived miR-631 targeting and regulating E2F family of transcription factor 2 (E2F2) to repress the malignant behavior of NSCLC cells. Test of microRNA (miR)-631 and E2F2 in NSCLC was performed. BMSCs-Exo that altered miR-631 was co-cultured with NSCLC cells. Detection of the cloning and progression of NSCLC cells was performed. Testification of the targeting of miR-631 with E2F2 was conducted. In vivo experiments were performed to verify the results in vitro . In short, elevation of miR-631 Exo repressed the advancement and phosphatidylinositol 3‐kinase/Akt activation of NSCLC cells, while silence of miR-631 was in the opposite. In terms of mechanism, miR-631 exerted the influence via targeting E2F2. The coincident results were obtained in animal models. In brief, BMSC-Exo mediated E2F2 via delivering miR-631 to NSCLC cells to modulate the malignant behavior of NSCLC.

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E2F2 inhibition induces autophagy via the PI3K/Akt/mTOR pathway in gastric cancer

Cited by 23 publications

References 45 publications

Identification of the Expression and Clinical Significance of E2F Family in Clear Cell Renal Cell Carcinoma

Identification of the Expression and Clinical Significance of E2F Family in Clear Cell Renal Cell Carcinoma

Comprehensive analysis of autophagy-related clusters and individual risk model for immunotherapy response prediction in gastric cancer

MicroRNA-631 deriving from bone marrow mesenchymal stem cell exosomes facilitates the malignant behavior of non-small cell lung cancer via modulating the E2F family of transcription factor 2/phosphatidylinositol 3‐kinase/Akt signaling pathway

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