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Long non-coding RNA SOX2OT promotes the stemness phenotype of bladder cancer cells by modulating SOX2
Long non-coding RNA SOX2OT promotes the stemness phenotype of bladder cancer cells by modulating SOX2
- Source :
- Molecular Cancer, Molecular Cancer, Vol 19, Iss 1, Pp 1-13 (2020)
- Publication Year :
- 2019
-
Abstract
- Background Accumulating evidence indicates that long non-coding RNAs (lncRNAs) are potential biomarkers and key regulators of tumour development and progression. SOX2 overlapping transcript (SOX2OT) is a novel lncRNA that acts as a potential biomarker and is involved in the development of cancer and cancer stem cells. However, the clinical significance and molecular mechanism of SOX2OT in bladder cancer are still unknown. Methods The expression level of SOX2OT was determined by RT-qPCR in a total of 106 patients with urothelial bladder cancer and in different bladder cancer cell (BCC) lines. Bladder cancer stem cells (BCSCs) were isolated from BCCs using flow cytometry based on the stem cell markers CD44 and ALDH1. Loss-of-function experiments were performed to investigate the biological roles of SOX2OT in the stemness phenotype of BCSCs. Comprehensive transcriptional analysis, RNA FISH, dual-luciferase reporter assays and western blots were performed to explore the molecular mechanisms underlying the functions of SOX2OT. Results SOX2OT was highly expressed in bladder cancer, and increased SOX2OT expression was positively correlated with a high histological grade, advanced TNM stage and poor prognosis. Further experiments demonstrated that knockdown of SOX2OT inhibited the stemness phenotype of BCSCs. Moreover, inhibition of SOX2OT delayed xenograft tumour growth and decreased metastases in vivo. Mechanistically, we found that SOX2OT was mainly distributed in the cytoplasm and positively regulated SOX2 expression by sponging miR-200c. Furthermore, SOX2 overexpression reversed the SOX2OT silencing-induced inhibition of the BCSC stemness phenotype. Conclusion This study is the first to demonstrate that SOX2OT plays an important regulatory role in BCSCs and that SOX2OT may serve as a potential diagnostic biomarker and therapeutic target in bladder cancer.
- Subjects :
- 0301 basic medicine
Male
Cancer Research
SOX2
Mice, Nude
Apoptosis
Stem cell marker
lcsh:RC254-282
miR-200c
03 medical and health sciences
Mice
0302 clinical medicine
Cancer stem cell
medicine
Biomarkers, Tumor
Tumor Cells, Cultured
Animals
Humans
Cell Proliferation
SOX2OT
Mice, Inbred BALB C
Bladder cancer
biology
SOXB1 Transcription Factors
Research
CD44
Cancer
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
Prognosis
Xenograft Model Antitumor Assays
Long non-coding RNA
Gene Expression Regulation, Neoplastic
MicroRNAs
030104 developmental biology
Oncology
Urinary Bladder Neoplasms
030220 oncology & carcinogenesis
biology.protein
Cancer research
Neoplastic Stem Cells
Molecular Medicine
Female
RNA, Long Noncoding
Stem cell
Subjects
Details
- ISSN :
- 14764598
- Volume :
- 19
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Molecular cancer
- Accession number :
- edsair.doi.dedup.....cd221c4aa798dacee7ca2cbba72eaa5c