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Circ_0089823 reinforces malignant behaviors of non-small cell lung cancer by acting as a sponge for microRNAs targeting SOX4
- Source :
- Neoplasia (New York, N.Y.), Neoplasia: An International Journal for Oncology Research, Vol 23, Iss 9, Pp 887-897 (2021)
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- In recent years, increasing evidence indicates the significant roles of circRNAs in carcinogenesis. However, their roles in lung cancer remain largely unclear. We profiled the circRNA expression in 10 paired non-small cell lung cancer (NSCLC) and adjacent non-cancer tissues using high-throughput sequencing. A total of 183 up-regulated and 428 down-regulated circRNAs were identified in the NSCLC tissues (fold change ≥ 2, P < 0.05). Circ_0089823, an up-regulated circRNA (5.4-fold, P = 0.0017), was further investigated through loss-of-function and gain-of-function. The circ_0089823 level in NSCLC samples was related to the gender, tumor size, pathological type, TNM stage and smoking history. Knockdown of circ_0089823 suppressed cell proliferation, induced cell cycle arrest and apoptosis of NSCLC cells in vitro. Additionally, circ_0089823-silenced xenografts grew much slowly. On the contrary, its over-expression promoted the malignant behaviors of NSCLC cells. Furthermore, SOX4, a tumor-promoting transcription factor, was highly expressed in NSCLC tissues and positively regulated by circ_0089823. Bioinformatic analysis revealed several potential binding sites for miR-507, miR-557, miR-579-3p and miR-1287-5p in circ_0089823 and SOX4 3′-untranslated region, which was later confirmed by luciferase reporter assay. Interestingly, silencing SOX4 countervailed the effects of circ_0089823 over-expression on NSCLC cells. Here, we revealed that circ_0089823 might act as a sponge of microRNAs targeting SOX4, thus increasing the expression of SOX4, thereby reinforcing the malignant behaviors of NSCLC cells. This study indicates that circ_0089823 has the potential to become a candidate target for NSCLC treatment.
- Subjects :
- Male
Untranslated region
Cancer Research
Lung Neoplasms
Cell cycle checkpoint
Circ_0089823
Proliferation
Apoptosis
FISH, RNA fluorescence in situ hybridization
medicine.disease_cause
miR, microRNA
AUC, area under the curve
Non-small cell lung cancer
ARSE, arylsulfatase E
Carcinoma, Non-Small-Cell Lung
RC254-282
Mice, Inbred BALB C
HBE, human bronchial epithelial cells
qPCR, quantitative real-time PCR
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
MicroRNA
Middle Aged
Tumor Burden
UTR, untranslated region
SOX4
Female
FITC, fluorescein isothiocyanate
circRNAs, circular RNA
Original article
Mice, Nude
Biology
SOXC Transcription Factors
PI, propidium iodide
CCK-8, cell counting kit-8
FBS, fetal bovine serum
KEGG, kyoto encyclopedia of genes and genomes
NSCLC, non-small cell lung cancer
SOX4, sex-determining region Y-box 4
microRNA
medicine
Animals
Humans
Gene silencing
Lung cancer
GO, gene ontology
Aged
TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling
Sequence Analysis, RNA
Cell growth
Gene Expression Profiling
RNA, Circular
medicine.disease
Xenograft Model Antitumor Assays
ROC, receiver operating characteristic
respiratory tract diseases
MicroRNAs
HEK293 Cells
A549 Cells
Cancer research
gDNA, genomic DNA
Carcinogenesis
DAPI, 4′,6-diamidino-2-phenylindole
Subjects
Details
- ISSN :
- 14765586
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Neoplasia
- Accession number :
- edsair.doi.dedup.....9425d498cf36f839efaa5e73ee683759