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

• Published in: PLoS genetics 2016-07, Vol.12 (7), p.e1006183-e1006183
• Main Authors: Li, Yingqin, Tang, Xinran, He, Qingmei, Yang, Xiaojing, Ren, Xianyue, Wen, Xin, Zhang, Jian, Wang, Yaqin, Liu, Na, Ma, Jun
• Format: Article
• Language: English
• Subjects: Adult; Aged; Animals; Apoptosis; Biology and Life Sciences; Cancer; Cancer metastasis; Cancer therapies; Carcinoma; Cell growth; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic - genetics; Cytochrome; Cytochromes c - metabolism; Cytosol - metabolism; Development and progression; Disease Progression; Experiments; Female; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Health aspects; Humans; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Kinases; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Medicine and Health Sciences; Membrane Potentials; Mice; Mice, Inbred BALB C; MicroRNA; MicroRNAs - metabolism; Middle Aged; Mitochondria; Mitochondria - enzymology; Mitochondria - metabolism; Nasopharyngeal cancer; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms - metabolism; Nasopharyngeal Neoplasms - pathology; Neoplasm Metastasis; Proportional Hazards Models; Protein expression; Proteins; Research and Analysis Methods; Signal Transduction; Tumorigenesis
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1006183

The therapeutic strategy for advanced nasopharyngeal carcinoma (NPC) is still challenging. It is an urgent need to uncover novel treatment targets for NPC. Therefore, understanding the mechanisms underlying NPC tumorigenesis and progression is essential for the development of new therapeutic strategies. Here, we showed that TP53-regulated inhibitor of apoptosis (TRIAP1) was aberrantly overexpressed and associated with poor survival in NPC patients. TRIAP1 overexpression promoted NPC cell proliferation and suppressed cell death in vitro and in vivo, whereas TRIAP1 knockdown inhibited cell tumorigenesis and enhanced apoptosis through the induction of mitochondrial fragmentation, membrane potential alteration and release of cytochrome c from mitochondria into the cytosol. Intersecting with our previous miRNA data and available bioinformatic algorithms, miR-320b was identified and validated as a negative regulator of TRIAP1. Further studies showed that overexpression of miR-320b suppressed NPC cell proliferation and enhanced mitochondrial fragmentation and apoptosis both in vitro and in vivo, while silencing of miR-320b promoted tumor growth and suppressed apoptosis. Additionally, TRIAP1 restoration abrogated the proliferation inhibition and apoptosis induced by miR-320b. Moreover, the loss of miR-320b expression was inversely correlated with TRIAP1 overexpression in NPC patients. This newly identified miR-320b/TRIAP1 pathway provides insights into the mechanisms leading to NPC tumorigenesis and unfavorable clinical outcomes, which may represent prognostic markers and potential therapeutic targets for NPC treatment.