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Overexpression of Mitochondria Mediator Gene TRIAP1 by miR-320b Loss Is Associated with Progression in Nasopharyngeal Carcinoma
- Source :
- PLoS Genetics, PLoS Genetics, Vol 12, Iss 7, p e1006183 (2016)
- Publication Year :
- 2016
- Publisher :
- Public Library of Science (PLoS), 2016.
-
Abstract
- 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.<br />Author Summary The therapeutic strategy for advanced nasopharyngeal carcinoma (NPC) is still challenging. The most urgent need for NPC is novel treatment targets. Therefore, understanding the mechanisms underlying NPC tumorigenesis and progression is essential for the development of new therapeutic strategies. Here, we identified TRIAP1 could serve as a prognostic biomarker in NPC, and function as an oncogene in NPC tumorigenesis and mitochondrial apoptosis through inhibiting the release of cytochrome c. Moreover, miR-320b post-transcriptionally regulated TRIAP1 expression, and exhibited inhibitory effects on proliferation and promoted apoptosis through targeting TRIAP1. Thus, our study provides new insights into the mechanisms of NPC tumorigenesis and progression and identifies novel therapeutic targets for NPC treatment.
- Subjects :
- Male
0301 basic medicine
Cancer Research
Carcinogenesis
Cell
Apoptosis
Biochemistry
Membrane Potentials
Mice
Cytosol
0302 clinical medicine
Medicine and Health Sciences
Neoplasm Metastasis
Energy-Producing Organelles
Genetics (clinical)
Staining
Mice, Inbred BALB C
Nasopharyngeal Carcinoma
Cell Death
Liver Neoplasms
Intracellular Signaling Peptides and Proteins
Cytochromes c
Cell Staining
Middle Aged
Mitochondria
Cell biology
Gene Expression Regulation, Neoplastic
Nucleic acids
Cell Transformation, Neoplastic
medicine.anatomical_structure
Oncology
Cell Processes
030220 oncology & carcinogenesis
Disease Progression
Female
Cellular Structures and Organelles
Signal Transduction
Research Article
Adult
Programmed cell death
lcsh:QH426-470
Nasopharyngeal neoplasm
Bioenergetics
Biology
Research and Analysis Methods
Inhibitor of apoptosis
Carcinomas
03 medical and health sciences
Cell Line, Tumor
otorhinolaryngologic diseases
Genetics
medicine
Animals
Humans
Gene silencing
Non-coding RNA
Molecular Biology
Ecology, Evolution, Behavior and Systematics
Aged
Cell Proliferation
Proportional Hazards Models
Cell growth
Carcinoma
Cancers and Neoplasms
Biology and Life Sciences
Nasopharyngeal Neoplasms
Cell Biology
medicine.disease
Gene regulation
lcsh:Genetics
MicroRNAs
stomatognathic diseases
030104 developmental biology
Nasopharyngeal carcinoma
Specimen Preparation and Treatment
RNA
Gene expression
Subjects
Details
- ISSN :
- 15537404
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- PLOS Genetics
- Accession number :
- edsair.doi.dedup.....fd097242bd00320a0fc087addc461185