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Long Noncoding RNA SOX2-OT Knockdown Inhibits Proliferation and Metastasis of Prostate Cancer Cells Through Modulating the miR-452-5p/HMGB3 Axis and Inactivating Wnt/β-Catenin Pathway
- Source :
- Cancer Biotherapy and Radiopharmaceuticals. 35:682-695
- Publication Year :
- 2020
- Publisher :
- Mary Ann Liebert Inc, 2020.
-
Abstract
- Background: Recent studies have proven that abnormal expression of long noncoding RNAs (lncRNAs) often contributes to growth and invasion of cancer cells. The purpose of this study was to investigate the biological function and regulatory mechanism of lncRNA SOX2 overlapping transcript (SOX2-OT) in prostate cancer (PCa) progression. Materials and Methods: The expression of SOX2-OT, microRNA-452-5p (miR-452-5p), and high mobility group box 3 (HMGB3) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Flow cytometry was performed to determine the cell cycle distribution. Western blot assay was conducted to measure the protein levels of cyclin D1, p21, p27, E-cadherin, vimentin, and N-cadherin. The interaction between miR-452-5p and SOX2-OT or HMGB3 was predicted by bioinformatics analysis and verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. The mice xenograft model was established to investigate the role of SOX2-OT in vivo. Results: SOX2-OT and HMGB3 were upregulated, whereas miR-452-5p was downregulated in PCa tissues and cells. Knockdown of SOX2-OT inhibited PCa cell growth and metastasis. MiR-452-5p could directly bind to SOX2-OT and its knockdown reversed the inhibitory effects of SOX2-OT interference on growth and metastasis of PCa cells. HMGB3 was a direct target of miR-452-5p and its knockdown weakened the promotive effects of miR-452-5p silence on growth and metastasis of PCa cells. Moreover, HMGB3 expression was inversely regulated by miR-452-5p and positively modulated by SOX2-OT. Furthermore, SOX2-OT activated the Wnt/β-catenin signaling pathway through increasing HMGB3 expression. Finally, SOX2-OT knockdown hindered tumor growth in vivo by regulating miR-452-5p/HMGB3 axis. Conclusions: SOX2-OT downregulation limited PCa cell growth and metastasis by regulating miR-452-5p/HMGB3 axis and inactivating Wnt/β-catenin signaling pathway, which might offer lncRNA-directed diagnosis and therapy for PCa.
- Subjects :
- Male
0301 basic medicine
Cancer Research
Metastasis
Mice
03 medical and health sciences
0302 clinical medicine
SOX2
Cell Line, Tumor
HMGB3 Protein
medicine
Animals
Humans
Radiology, Nuclear Medicine and imaging
Wnt Signaling Pathway
beta Catenin
Prostatectomy
Pharmacology
Gene knockdown
Chemistry
Cell growth
Prostate
Wnt signaling pathway
Computational Biology
Prostatic Neoplasms
General Medicine
Cell cycle
medicine.disease
Xenograft Model Antitumor Assays
Gene Expression Regulation, Neoplastic
MicroRNAs
030104 developmental biology
Oncology
Gene Knockdown Techniques
030220 oncology & carcinogenesis
Catenin
Cancer cell
Cancer research
RNA, Long Noncoding
Subjects
Details
- ISSN :
- 15578852 and 10849785
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- Cancer Biotherapy and Radiopharmaceuticals
- Accession number :
- edsair.doi.dedup.....9ecd640618bc32a8523f2a4c64191a30