Overexpression of Mitochondria Mediator Gene TRIAP1 by miR-320b Loss Is Associated with Progression in Nasopharyngeal Carcinoma

Li, Ying‐Qin; Tang, Xixiang; He, Qing‐Mei; Yang, Xiaojing; Ren, Xianyue; Wen, Xin; Zhang, Jian; Wang, Yaqin; Liu, Na; Ma, Jun

doi:10.1371/journal.pgen.1006183

Cited by 55 publications

(64 citation statements)

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“…A report describes that TRIAP1 is up-regulated in drug-resistant breast cancer cells and altered expression of TRIAP1 changes cellular sensitivity to doxorubicin in breast cancer [29]. MiR-320b-inhibited TRIAP1 is involved in progression in nasopharyngeal carcinoma [30]. Our data take a further step to the function of TRIAP1 in lung cancer.…”

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

confidence: 52%

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

confidence: 52%

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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“…unveiled that TRIAP1 (secreted by fibroblasts) was taken up by adjacent prostate cancer cells, PC3 and LNCaP, resulting in a pronounced cancer radioresistance . Studies have illustrated that TRIAP1 exerts antiapoptotic effects via its interaction with HSP70, which inhibits cytochrome c to activate the apoptotic protease activating factor 1 and in turn the downstream caspase‐9 . Moreover, we discovered that TRIAP1 is involved in the upregulation of several antioxidant proteins, which can help remove radiation‐induced ROS.…”

Section: Discussionmentioning

confidence: 91%

“…Previous studies demonstrated that both microRNA‐18a and microRNA‐320b target TRIAP1. Of note, abnormal downregulation of these microRNAs results in an elevated TRIAP1 expression, thus promoting the progression of ovarian cancer and nasopharyngeal carcinoma . The scientific consensus states that the cancer‐promoting role of TRIAP1 is probably associated with its inhibitory effect on apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Whereas TP53 is a well-known tumor suppressor, TRIAP1 functions as an oncogene because it mechanistically inhibits the interaction of cytochrome c with the apoptotic protease activating factor 1, thus preventing cancer cell apoptosis. 4,5 A previous transcriptomics study found that radiation significantly increased TRIAP1 expression in A549 cells. 6 Furthermore, gene set enrichment analysis (GSEA) in this study highlighted an implication of TRIAP1 in the regulation of redox homeostasis, which implies that TRIAP1 might be linked to the radioresistance of NSCLC cells by maintaining redox homeostasis.…”

Section: Introductionmentioning

confidence: 98%

“…TP53‐regulated inhibitor of apoptosis 1 (TRIAP1) is an evolutionarily conserved protein, mainly regulated by TP53. Whereas TP53 is a well‐known tumor suppressor, TRIAP1 functions as an oncogene because it mechanistically inhibits the interaction of cytochrome c with the apoptotic protease activating factor 1, thus preventing cancer cell apoptosis . A previous transcriptomics study found that radiation significantly increased TRIAP1 expression in A549 cells .…”

Section: Introductionmentioning

confidence: 99%

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TRIAP1 knockdown sensitizes non‐small cell lung cancer to ionizing radiation by disrupting redox homeostasis

et al. 2020

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Background Radioresistance of some non‐small cell lung cancer (NSCLC) types increases the risk of recurrence or metastasis in afflicted patients, following radiotherapy. As such, further improvements to NSCLC radiotherapy are needed. The expression of oncogene TP53‐regulated inhibitor of apoptosis 1 (TRIAP1) in NSCLC is increased following irradiation. Furthermore, gene set enrichment analysis (GSEA) has suggested that TRIAP1 might be involved in maintaining redox homeostasis. This in turn might enhance cell radioresistance. Methods In this study we irradiated human NSCLC cell lines (A549 and H460), while knocking down TRIAP1, to determine whether a disrupted redox homeostasis could attenuate radioresistance. Results Irradiation notably increased both mRNA and protein levels of TRIAP1. In addition, TRIAP1 knockdown decreased the expression of several antioxidant proteins, including thioredoxin‐related transmembrane protein (TMX) 1, TMX2, thioredoxin (TXN), glutaredoxin (GLRX) 2, GLRX3, peroxiredoxin (PRDX) 3, PRDX4, and PRDX6 in A549 and H460 cells. In addition, silencing TRIAP1 impaired the radiation‐induced increase of the aforementioned proteins. Continuing along this line, we observed a radiation‐induced reduction of cell viability and invasion, as well as increased apoptosis and intracellular reactive oxygen species following TRIAP1 knockdown. Conclusions In summary, we identified TRIAP1 as a key contributor to the radioresistance of NSCLC by maintaining redox homeostasis.

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Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies

Shen¹,

Wang²,

Mao³

et al. 2023

MedComm

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Tumor suppressor p53 can transcriptionally activate downstream genes in response to stress, and then regulate the cell cycle, DNA repair, metabolism, angiogenesis, apoptosis, and other biological responses. p53 has seven functional domains and 12 splice isoforms, and different domains and subtypes play different roles. The activation and inactivation of p53 are finely regulated and are associated with phosphorylation/acetylation modification and ubiquitination modification, respectively. Abnormal activation of p53 is closely related to the occurrence and development of cancer. While targeted therapy of the p53 signaling pathway is still in its early stages and only a few drugs or treatments have entered clinical trials, the development of new drugs and ongoing clinical trials are expected to lead to the widespread use of p53 signaling‐targeted therapy in cancer treatment in the future. TRIAP1 is a novel p53 downstream inhibitor of apoptosis. TRIAP1 is the homolog of yeast mitochondrial intermembrane protein MDM35, which can play a tumor‐promoting role by blocking the mitochondria‐dependent apoptosis pathway. This work provides a systematic overview of recent basic research and clinical progress in the p53 signaling pathway and proposes that TRIAP1 is an important therapeutic target downstream of p53 signaling.

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Overexpression of Mitochondria Mediator Gene TRIAP1 by miR-320b Loss Is Associated with Progression in Nasopharyngeal Carcinoma

Cited by 55 publications

References 51 publications

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

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

TRIAP1 knockdown sensitizes non‐small cell lung cancer to ionizing radiation by disrupting redox homeostasis

Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies

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