BIM-mediated apoptosis and oncogene addiction

Li, Yulin; Deutzmann, Anja; Felsher, Dean W.

doi:10.18632/aging.101072

Cited by 5 publications

(3 citation statements)

References 7 publications

(10 reference statements)

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“…Furthermore, p27 is a CDK inhibitor that has a negative regulatory effect on proliferation and is a downstream target of FOXO1; consequently, FOXO1 inhibits cell proliferation by upregulating p27 (39)(40)(41)(42). The Bim protein belongs to the Bcl-2 protein family and exerts a pro-apoptotic effect on cells (43,44); previous studies have confirmed that FOXO1 regulates cell apoptosis through its downstream targets, including Bim (45,46). The present study confirmed that propofol may regulate miR-374a/FOXO1 signaling to promote the expression of p27 and Bim, and to inhibit the proliferation and promote the apoptosis of ovarian cancer cells, thereby enhancing the sensitivity of ovarian cancer cells to ddP.…”

Section: Discussionmentioning

confidence: 99%

Propofol inhibits proliferation and cisplatin resistance in ovarian cancer cells through regulating the microRNA‑374a/forkhead box O1 signaling axis

Sun¹,

Peng²,

et al. 2020

Mol Med Report

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ovarian cancer is a prominent disease that demonstrates high incidence rates in women and often presents multidrug resistance. Propofol has been demonstrated to suppress the malignancy of various types of human cancer; however, the underlying molecular mechanisms of propofol in ovarian cancer remain largely unknown. The present study aimed to investigate whether and how propofol inhibits proliferation and cisplatin (ddP) resistance in ovarian cancer cells. ovarian cancer cell viability was assessed by the cell counting kit-8 assay; apoptosis and cell cycle progression were determined by flow cytometry; the relative expression levels of microRNA (miR)-374a and forkhead box O1 (FOXO1) were analyzed using reverse transcription-quantitative Pcr; the binding ability of miR-374a to FOXO1 was assessed by the dual-luciferase reporter assay; cellular sensitivity to ddP was detected using the MTT assay; and finally, the protein expression levels of FOXO1, p27, and Bcl-2-like-protein 11 (Bim) were analyzed by western blotting. Propofol reduced viability, promoted apoptosis and decreased mir-374a expression levels in A2780 cells. In addition, the viability of a2780/ddP cells in the propofol + ddP treatment group was significantly inhibited, and the apoptotic rate was increased. In addition, miR-374a overexpression increased cell viability and the proportion of cells in the S phase, and decreased the proportion of cells in the G0/G1 phase. conversely, genetic knockdown of miR-374a exerted the opposite effects on cell viability and cell cycle progression. Moreover, mir-374a was demonstrated to bind to FOXO1. Propofol promoted the expression of FOXO1, p27 and Bim, induced cell cycle arrest and decreased ovarian cancer cell viability. in addition, treatment with propofol and DDP regulated FOXO1 and increased apoptosis of ovarian cancer cells. in conclusion, propofol downregulated mir-374a and modulated the FOXO1 pathway to reduce proliferation and DDP resistance in ovarian cancer cells.

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Section: Discussionmentioning

confidence: 99%

Propofol inhibits proliferation and cisplatin resistance in ovarian cancer cells through regulating the microRNA‑374a/forkhead box O1 signaling axis

Sun¹,

Peng²,

et al. 2020

Mol Med Report

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“…it is an important regulatory protein of apoptosis and is stable in the homeostasis of hematopoietic cells, preventing autoimmunity and tumorigenesis (14). Bim is widely expressed in normal cells and exists in a variety of isomers (15). certain apoptotic stimuli can activate Bim molecules through various signaling pathways (16).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑25‑3p regulates human nucleus pulposus cell proliferation and apoptosis in intervertebral disc degeneration by targeting Bim

Zhao¹,

Zheng²,

Ye³

et al. 2020

Mol Med Rep

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intervertebral disc degeneration (idd) is a degenerative disease of the spine originating from the intervertebral disc. Micrornas (mirnas or mirs) are a group of endogenous small non-coding rnas that act on target genes and play a critical role in numerous biological processes. However, the underlying mechanism of mir-25-3p in idd remains unclear. Therefore, the present study aimed to explore the role of mir-25-3p in the pathogenesis of idd. The results demonstrated that mir-25-3p was downregulated in rat degenerative nucleus pulposus (nP) cells and that Bcl-2 interacting mediator of cell death (Bim) was a direct target of mir-25-3p. next, to investigate the effect of mir-25-3p on normal nP cell proliferation and apoptosis, nP cells were transfected with an mir-25-3p inhibitor, a negative control of mir-25-3p inhibitor, mir-25-3p inhibitor + control-small interference rna (sirna) or mir-25-3p inhibitor + Bim-sirna for 48 h and cell proliferation and apoptosis were then analyzed. The results demonstrated that the mir-25-3p inhibitor could decrease nP cell proliferation and induce cell apoptosis, and these effects were reversed by Bim-sirna. in addition, an in vitro cell model of idd was established by subjecting nP cells to 10 ng/ml interleukin (il)-1β for 24 h. Further experiments suggested that il-1β treatment induced a reduction in nP cell proliferation and an increase in cell apoptosis, which were prevented by the mir-25-3p mimic. all the effects of mir-25-3p mimic on il-1β-treated NP cells were significantly reversed by Bim upregulation. These findings suggested that miR-25-3p may be a novel therapeutic target for idd prevention.

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“…BART miRNAs can also regulate proteins that interact with each other, such as the pro-apoptotic proteins PUMA, BIM, and BAD [52]. PUMA, also known as BCL-2 binding component 3 (BBC3), binds to all antiapoptotic members [53], and can be suppressed by miR-BART5.…”

Section: Epstein-barr Virus (Ebv)mentioning

confidence: 99%

MicroRNAs Encoded by Virus and Small RNAs Encoded by Bacteria Associated with Oncogenic Processes

Serafín-Higuera¹,

Leija-Montoya²,

Leija-Montoya

et al. 2021

Processes

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Cancer is a deadly disease and, globally, represents the second leading cause of death in the world. Although it is a disease where several factors can help its development, virus induced infections have been associated with different types of neoplasms. However, in bacterial infections, their participation is not known for certain. Among the proposed approaches to oncogenesis risks in different infections are microRNAs (miRNAs). These are small molecules composed of RNA with a length of 22 nucleotides capable of regulating gene expression by directing protein complexes that suppress the untranslated region of mRNA. These miRNAs and other recently described, such as small RNAs (sRNAs), are deregulated in the development of cancer, becoming promising biomarkers. Thus, resulting in a study possibility, searching for new tools with diagnostic and therapeutic approaches to multiple oncological diseases, as miRNAs and sRNAs are main players of gene expression and host–infectious agent interaction. Moreover, sRNAs with limited complementarity are similar to eukaryotic miRNAs in their ability to modulate the activity and stability of multiple mRNAs. Here, we will describe the regulatory RNAs from viruses that have been associated with cancer and how sRNAs in bacteria can be related to this disease.

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BIM-mediated apoptosis and oncogene addiction

Cited by 5 publications

References 7 publications

Propofol inhibits proliferation and cisplatin resistance in ovarian cancer cells through regulating the microRNA‑374a/forkhead box O1 signaling axis

Propofol inhibits proliferation and cisplatin resistance in ovarian cancer cells through regulating the microRNA‑374a/forkhead box O1 signaling axis

MicroRNA‑25‑3p regulates human nucleus pulposus cell proliferation and apoptosis in intervertebral disc degeneration by targeting Bim

MicroRNAs Encoded by Virus and Small RNAs Encoded by Bacteria Associated with Oncogenic Processes

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