RB1 dual role in proliferation and apoptosis: Cell fate control and implications for cancer therapy

Indovina, Paola; Pentimalli, Francesca; Casini, Nadia; Vocca, Immacolata; Giordano, Antonio

doi:10.18632/oncotarget.4286

Cited by 136 publications

(125 citation statements)

References 132 publications

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“…Thus, the results implied the significance of E2F target regulation by EPEL in lung cancer. E2F promotes various cancer-related functions, such as cell cycle progression and metabolism, while also promoting opposite cancer-related functions, such as apoptosis, according to its binding partners [30,54]. Roworth et al reported that each E2F function (cell cycle progression, metabolism, or apoptosis) is associated with its corresponding target genes [30].…”

Section: Regulation Of E2f Target and Cell Cycle-related Genes By Epelmentioning

confidence: 99%

The LncRNA EPEL Promotes Lung Cancer Cell Proliferation Through E2F Target Activation

Park

Choi

Bae

et al. 2018

Cell Physiol Biochem

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Background/Aims: Recent studies have revealed that many long non-coding RNAs (lncRNAs) play oncogenic or tumor-suppressive roles in various cancers. Lung cancer is the leading cause of cancer-related death worldwide, and many lung cancer patients frequently relapse after surgery, even those in the early stages. However, the oncogenic or tumor-suppressive roles and clinical implications of lncRNAs in lung cancer have not been fully elucidated. Methods:The association between an E2F-mediated cell proliferation enhancing lncRNA (EPEL) expression and lung cancer patient survival was accessed using public microarray data with clinical information. Cancer-related phenotypes were analyzed by the siRNA knockdown of EPEL in two lung cancer cell lines. Gene set analysis of gene expression data were performed to identify pathways regulated by EPEL. RNA immunoprecipitation, RT-qPCR, and ChIP assays were performed to explore the functions of selected target genes regulated by EPEL. Results: EPEL, known as LOC90768 and MGC45800, was associated with the relapse and survival of lung cancer patients and promoted lung cancer cell proliferation through the activation of E2F target genes. EPEL knockdown specifically down-regulated the expression of cell cyclerelated E2F target genes, including Cyclin B1 (CCNB1), in lung cancer cells but not that of apoptosis-or metabolism-related E2F target genes. EPEL interacted with E2F1 and regulated the expression of the E2F target genes by changing the binding efficiency of E2F1 to the E2F target promoters. Moreover, the expression levels of EPEL and CCNB1 both alone and in combination were robust prognostic markers for lung cancer. Conclusions: Considering its specific effects on cell cycle-related E2F target genes and its significant association with the prognosis of lung cancer patients, we suggest that the transcriptional regulation of EPEL through E2F target genes is potentially a target for the development of novel therapeutic strategies for lung cancer patients.

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Section: Regulation Of E2f Target and Cell Cycle-related Genes By Epelmentioning

confidence: 99%

The LncRNA EPEL Promotes Lung Cancer Cell Proliferation Through E2F Target Activation

Park

Choi

Bae

et al. 2018

Cell Physiol Biochem

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“…Briefly, 1x10 6 cells/well were washed with PBS and resuspended in 500 µl binding buffer containing 2.5 µl annexin V-FITC and 5 µl PI. The cells samples were subjected to flow cytometry using a FACSCalibur flow cytometer and analyzed using CellQuest™ software (version 5.1; BD Biosciences).…”

Section: Apoptosis Analysismentioning

confidence: 99%

“…Induction of cell cycle arrest at different cell cycle checkpoints contributes to various antitumor effects (5). The induction of apoptosis, which typically involves the activation of various caspases, including caspase-3, represents an important underlying mechanism for the elimination of tumor cells (6).…”

Section: Introductionmentioning

confidence: 99%

Arctigenin, a natural lignan compound, induces G0/G1 cell cycle arrest and apoptosis in human glioma cells

et al. 2016

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Abstract.The aim of the current study was to investigate the anticancer potential of arctigenin, a natural lignan compound, in malignant gliomas. The U87MG and T98G human glioma cell lines were treated with various concentrations of arctigenin for 48 h and the effects of arctigenin on the aggressive phenotypes of glioma cells were assessed. The results demonstrated that arctigenin dose-dependently inhibited the growth of U87MG and T98G cells, as determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and bromodeoxyuridine incorporation assays. Arctigenin exposure also induced a 60-75% reduction in colony formation compared with vehicle-treated control cells. However, arctigenin was not observed to affect the invasiveness of glioma cells. Arctigenin significantly increased the proportion of cells in the G 0 /G 1 phase and reduced the number of cells in the S phase, as compared with the control group (P<0.05). Western blot analysis demonstrated that arctigenin increased the expression levels of p21, retinoblastoma and p53 proteins, and significantly decreased the expression levels of cyclin D1 and cyclin-dependent kinase 4 proteins. Additionally, arctigenin was able to induce apoptosis in glioma cells, coupled with increased expression levels of cleaved caspase-3 and the pro-apoptotic BCL2-associated X protein. Furthermore, arctigenin-induced apoptosis was significantly suppressed by the pretreatment of cells with Z-DEVD-FMK, a caspase-3 inhibitor. In conclusion, the results suggest that arctigenin is able to inhibit cell proliferation and may induce apoptosis and cell cycle arrest at the G 0 /G 1 phase in glioma cells. These results warrant further investigation of the anticancer effects of arctigenin in animal models of gliomas.

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“…Several studies on different cancer types have previously examined how RB1 status affects tumor sensitivity to treatments and clinical outcome. The disruption of Rb1 function enhances response to DNA-damaging agents in breast, prostate, bladder, hepatocellular and ovarian cancer as well as in childhood acute lymphoblastic leukemia (14). In SCLC, a major prognostic factor, quite useful as a predictor for long-term survival, is the female sex, especially when restricted to younger patients (15).…”

mentioning

confidence: 99%

Unraveling the genomic complexity of small cell lung cancer

Karachaliou¹,

Sosa²,

Rosell³

2016

Transl. Lung Cancer Res.

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RB1 dual role in proliferation and apoptosis: Cell fate control and implications for cancer therapy

Cited by 136 publications

References 132 publications

The LncRNA EPEL Promotes Lung Cancer Cell Proliferation Through E2F Target Activation

The LncRNA EPEL Promotes Lung Cancer Cell Proliferation Through E2F Target Activation

Arctigenin, a natural lignan compound, induces G0/G1 cell cycle arrest and apoptosis in human glioma cells

Unraveling the genomic complexity of small cell lung cancer

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