miR-125b suppresses oral oncogenicity by targeting the anti-oxidative gene PRXL2A

Autor: Shu Chun Lin, Yun Yen Wei, Chung Hsien Chou, Kuo Wei Chang, Li Yin Yeh, Cheng Chieh Yang, Yi Fen Chen, Chung Ji Liu
Rok vydání: 2018
Předmět:
0301 basic medicine
IHC
Immunohistochemistry
ANE
Areca nut extract
Carcinogenesis
Clinical Biochemistry
Ct
threshold cycle
FAM213A
Family with sequence similarity 213
member A
medicine.disease_cause
Biochemistry
HNSCC
law.invention
Pathogenesis
AUC
area under the curve
0302 clinical medicine
law
Genes
Reporter
NCMT
non-cancerous matched tissue
lcsh:QH301-705.5
DNPH
2
4-Dinitrophenylhydrazine
OSCC
Oral squamous cell carcinoma
lcsh:R5-920
Effector
CDDP
cisplatin
ISH
In situ hybridization
Scr
scramble
miR-125
Gene Expression Regulation
Neoplastic
Phenotype
TRX
thioredoxin
Gene Knockdown Techniques
H2O2
hydrogen peroxide
Mouth Neoplasms
PRXL2A
Peroxiredoxin like 2A
lcsh:Medicine (General)
Research Paper
wt
wild-type
ARE
antioxidant response element
Biology
NRF2
OS
overall survival
03 medical and health sciences
Downregulation and upregulation
Cell Line
Tumor
microRNA
Oxidation
HNSCC
Head and neck squamous cell carcinoma
medicine
TMA
tissue microarray
Humans
Cell Proliferation
NRF2
Nuclear factor (erythroid-derived 2)-like 2
Organic Chemistry
Peroxiredoxin like 2A
Cancer
CDS
coding sequence
NAC
N-acetyl-l-cysteine
Peroxiredoxins
medicine.disease
miRNAs
MicroRNAs
ROC
receiver operating characteristic
PRX
Peroxiredoxin
stomatognathic diseases
MicroRNAs
Oxidative Stress
030104 developmental biology
lcsh:Biology (General)
ROC Curve
Cancer research
3′UTR
3′ untranslated region
Suppressor
TCGA
The Cancer Genome Atlas
Cisplatin
qPCR
quantitative PCR
Peroxiredoxin
Reactive Oxygen Species
030217 neurology & neurosurgery
Oxidative stress
ROS
Reactive oxygen species
Zdroj: Redox Biology
Redox Biology, Vol 22, Iss, Pp-(2019)
ISSN: 2213-2317
Popis: Oral squamous cell carcinoma (OSCC) is a globally prevalent malignancy. The molecular mechanisms of this cancer are not well understood and acquire elucidation. Peroxiredoxin like 2A (PRXL2A) has been reported to be an antioxidant protein that protects cells from oxidative stress. Our previous study identified an association between PRXL2A upregulation in OSCC and a worse patient prognosis. MicroRNAs (miRNAs) are small non-coding RNAs that are involved in the modulation of biological/pathological properties. The miR-125 family of genes drive pluripotent regulation across a wide variety of cancers. In this study, we identify the oncogenic eligibility of PRXL2A and clarify miR-125b as its upstream regulator. Downregulation of miR-125b can be observed in OSCC tumors. Lower miR-125b expression in tumors results in a worse patient prognosis at the relatively early stage. Reporter assays are able to validate that PRXL2A is a direct target of miR-125b. Exogenous miR-125b expression in OSCC cells results in increased oxidative stress, increased drug sensitivity, and suppressor activity that is paralleled by the knockout of PRXL2A gene. The suppressor activity of miR-125b is able to be rescued by PRXL2A, which suggests the existence of a miR-125b-PRXL2A regulatory axis that is part of OSCC pathogenesis. Nuclear factor-erythroid 2-related factor 2 (NRF2) was found to be a downstream effector of the miR-125b-PRXL2A cascade. As a whole, this study has pinpointed novel clues demonstrating that downregulation of miR-125b suppressor underlies upregulation of PRXL2A in OSCC, and this then protects the affected tumor cells from oxidative stress. Keywords: HNSCC, miR-125, NRF2, Oxidation, Peroxiredoxin like 2A
Databáze: OpenAIRE
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