TP53 Regulated Inhibitor of Apoptosis 1 (TRIAP1) stable silencing increases late apoptosis by upregulation of caspase 9 and APAF1 in RPMI8226 multiple myeloma cell line

Fook-Alves, Veruska L.; Oliveira, Mariana Bleker de; Zanatta, Daniela B; Colleoni, Gisele W. B.

doi:10.1016/j.bbadis.2016.03.011

Cited by 26 publications

(25 citation statements)

References 12 publications

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“…A previous study indicated that TRIAP1 inhibition could induce cell apoptosis by upregulating caspase-9 and apoptotic protease-activating factor 1 (APAF1) (17). Therefore, whether caspase-9 and APAF1 were involved in regulating PLC/PRF/5 cell apoptosis by miR-125a-5p was investigated using western blots.…”

Section: Resultsmentioning

confidence: 99%

miRNA‑125a‑5p inhibits hepatocellular carcinoma cell proliferation and induces apoptosis by targeting TP53 regulated inhibitor of apoptosis 1 and Bcl‑2‑like‑2 protein

Ma³

2019

Exp Ther Med

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The present study aimed to investigate the role and underlying molecular mechanism of microRNA (miR)-125a-5p in hepatocellular carcinoma. The level of miR-125a-5p was detected using reverse transcription-quantitative polymerase chain reaction. TargetScan was used to investigate the association between miR-125a-5p and TP53-regulated inhibitor of apoptosis 1 (TRIAP1)/B cell lymphoma-2-like 2 protein (BCL2L2). Dual luciferase reporter assay was used to confirm this prediction. To investigate the role of miR-125a-5p in hepatocellular carcinoma (HCC) cells, miR-125a-5p was overexpressed in the human HCC cell line PLC/PRF/5 using miR-125a-5p mimics. Subsequently, cell proliferation, cell apoptosis and cell migration were studied using MTT assay, flow cytometry analysis and Transwell assay, respectively. Protein expression levels in the present study were measured by western blot analysis. Taken together, the present results suggested that miR-125a-5p was markedly downregulated in HCC cells. TRIAP1 and BCL2L2 were direct targets of miR-125a-5p and were upregulated in PLC/PRF/5 cells. miR-125a-5p upregulation inhibited PLC/PRF/5 cell viability and migration and induced cell apoptosis. In addition, miR-125a-5p overexpression increased the expression of caspase9 and apoptotic protease-activating factor 1. Notably, the present study revealed that all the effects on PLC/PRF/5 cells elicited by miR-125a-5p overexpression were eliminated by TRIAP1/BCL2L2 upregulation. In conclusion, miR-125a-5p was shown to be downregulated in hepatocellular carcinoma and its upregulation inhibited hepatocellular carcinoma cell growth and metastasis by targeting TRIAP1 and BCL2L2.

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Section: Resultsmentioning

confidence: 99%

miRNA‑125a‑5p inhibits hepatocellular carcinoma cell proliferation and induces apoptosis by targeting TP53 regulated inhibitor of apoptosis 1 and Bcl‑2‑like‑2 protein

Ma³

2019

Exp Ther Med

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“…Some genes including TRIAP1 are reported to be up-regulated and play a crucial role in multiple myeloma [25,26]. A genome-wide genetic screen in human cells indicates that TRIAP1 is a specific repressor of p21, one p53 target gene [27].…”

Section: Mir-107 Negatively Correlates With Triap1 In Clinical Lung Cmentioning

confidence: 99%

MiR-107 inhibits proliferation of lung cancer cells through regulating TP53 regulated inhibitor of apoptosis 1 (TRIAP1)

Wang

Zuo

et al. 2017

Open Life Sciences

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Conclusions: MiR-107 suppresses cell proliferation by targeting TRIAP1 in lung cancer. Our finding allows new insights into the mechanisms of lung cancer that is mediated by miR-107.Keywords: miR-107, TRIAP1, proliferation, lung cancer IntroductionLung cancer is the principle cause of global cancerassociated mortality accounting for about 1.59 million deaths every year worldwide [1, 2]. Most of those cases have non-small-cell lung cancer (NSCLC) [3].MicroRNAs (miRNAs) usually negatively modulate gene expression through mRNA cleavage or translational repression [4]. Normally, conserved miRNAs plays a part in many processes, such as cell proliferation, apoptosis, and metabolism. Numerous miRNAs play important roles in cancers as oncogenes or tumour suppressor genes [5][6][7][8][9][10]. MiR-107 is proven to be involved in many cancers, such as colon, breast, gastric, liver, and bladder [11][12][13][14][15][16][17]. It has been reported that miR-107 results in cell cycle arrest to suppress cell proliferation in lung adenocarcinoma [18]. Lowly-expressed miR-107 correlates with tumor development and patient survival in NSCLC [19]. However, it remains unclear how miR-107 works in lung cancer.In the current study, we explored the effect of miR-107 and its novel target gene on proliferation of lung cancer cells. Our findings indicate that TRIAP1 serves as a novel target gene of miR-107 in lung cancer A549 cells. MiR-107 restrains the proliferation of lung cancer cells through regulating TRIAP1. Our finding takes a further step into the mechanism of miR-107-associated lung cancer. Results: QRT-PCR analysis revealed that miR-107 inhibitor or miR-107 was successfully transfected into A549 cells. Western Blot indicated that miR-107 decreased the expression of TRIAP1 protein in the cells. In contrast, miR-107 inhibitor augmented the levels of TRIAP1 protein. Functionally, miR-107 inhibitor remarkably suppressed A549 cell proliferation, whereas, TRIAP1 siRNAs could abrogate the miR-107 inhibitorinduced proliferation of cells. Then, we validated that TRIAP1 was increased in clinical lung cancer samples. MiR-107 expression was negatively related to TRIAP1 expression in clinical lung cancer samples.

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“…One of these genes, P53CSV/TRIAP1 (TP53 regulated inhibitor of apoptosis 1), was overexpressed in more than 90% of MM cases. TRIAP1 activates apoptotic pathways through interaction with HSP70, preventing APAF-1 (apoptosis protease activating factor 1), cytochrome c , and caspase-9 apoptosome complex formation [ 8 , 9 ]. Overexpression of HSP70 may provide a selective advantage for tumor cell survival due in part to its ability to inhibit cell death through APAF-1 and caspase 9 [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Proteasome and heat shock protein 70 (HSP70) inhibitors as therapeutic alternative in multiple myeloma

et al. 2017

Self Cite

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HSP70 connects multiple signaling pathways that work synergistically to protect tumor cells from death by proteotoxic stress and represents a possible target to establish a new approach for multiple myeloma treatment. Therefore, bioluminescent cell lines RPMI8226-LUC-PURO and U266-LUC-PURO were treated with HSP70 (VER155008) and/or proteasome (bortezomib) inhibitors and immunodeficient mice were used for subcutaneous xenograft models to evaluate tumor growth reduction and tumor growth inhibition after treatment. Bioluminescence imaging was used to follow tumor response. Treatment with bortezomib showed ∼60% of late apoptosis in RPMI8226-LUC-PURO (without additional benefit of VER155008 in this cell line). However, U266-LUC-PURO showed ∼60% of cell death after treatment with VER155008 (alone or with bortezomib). RPMI8226-LUC-PURO xenograft presented tumor reduction by bioluminescence imaging after treatment with bortezomib, VER155008 or drug combination compared to controls. Treatment with bortezomib, alone or combined with VER155008, showed inhibition of tumor growth assessed by bioluminescence imaging after one week in both RPMI8226-LUC-PURO and U266-LUC-PURO cell lines when compared to controls. In conclusion, our study shows that the combination of proteasome and HSP70 inhibitors induced cell death in tumor cells in vitro (late apoptosis induction) and in vivo (inhibition of tumor growth) with special benefit in U266-LUC-PURO, bearing 17p deletion.

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TP53 Regulated Inhibitor of Apoptosis 1 (TRIAP1) stable silencing increases late apoptosis by upregulation of caspase 9 and APAF1 in RPMI8226 multiple myeloma cell line

Abstract: In the present study, we demonstrated effects of TRIAP1 silencing on RPMI8226 MM cell line and established its mechanism mediated through APAF1 and Caspase 9. No relevant effect was found after gene silencing in U266 cell line.

Cited by 26 publications

References 12 publications

miRNA‑125a‑5p inhibits hepatocellular carcinoma cell proliferation and induces apoptosis by targeting TP53 regulated inhibitor of apoptosis 1 and Bcl‑2‑like‑2 protein

miRNA‑125a‑5p inhibits hepatocellular carcinoma cell proliferation and induces apoptosis by targeting TP53 regulated inhibitor of apoptosis 1 and Bcl‑2‑like‑2 protein

MiR-107 inhibits proliferation of lung cancer cells through regulating TP53 regulated inhibitor of apoptosis 1 (TRIAP1)

Proteasome and heat shock protein 70 (HSP70) inhibitors as therapeutic alternative in multiple myeloma

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