1. lncRNA TPTEP1 inhibits stemness and radioresistance of glioma through miR‑106a‑5p‑mediated P38 MAPK signaling
- Author
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Rong‑Mou Zhang, Mei‑Li Yang, Ting Tang, and Ling‑Xing Wang
- Subjects
0301 basic medicine ,Cancer Research ,Cell ,Apoptosis ,Radiation Tolerance ,p38 Mitogen-Activated Protein Kinases ,Biochemistry ,MAPK14 ,0302 clinical medicine ,glioma ,Brain Neoplasms ,Articles ,Cell cycle ,Prognosis ,Gene Expression Regulation, Neoplastic ,microRNA-106a-5p ,radioresistance ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Disease Progression ,Neoplastic Stem Cells ,Molecular Medicine ,RNA, Long Noncoding ,Pseudogenes ,Signal Transduction ,MAP Kinase Signaling System ,Biology ,stemness ,03 medical and health sciences ,Cancer stem cell ,Cell Line, Tumor ,Glioma ,Radioresistance ,microRNA ,Genetics ,medicine ,Humans ,neoplasms ,Molecular Biology ,Cell Proliferation ,Oncogene ,PTEN Phosphohydrolase ,Membrane Proteins ,medicine.disease ,Molecular medicine ,nervous system diseases ,MicroRNAs ,transmembrane phosphatase with tensin homology pseudogene 1 ,030104 developmental biology ,Cancer research ,Neoplasm Recurrence, Local - Abstract
Glioma is diagnosed as the most common intracranial malignant tumor. Cancer stem cells determine stemness and radioresistance, and may facilitate glioma recurrence. The present study aimed to investigate whether the long non-coding RNA (lncRNA) transmembrane phosphatase with tensin homology pseudogene 1 (TPTEP1) regulated cell stemness and radioresistance of glioma, and determine the underlying molecular mechanism of TPTEP1 in the modulation of glioma progression. Cell and molecular biology techniques were applied for investigating the role of TPTEP1 in glioma cell lines, animal model, and clinical samples. The results demonstrated that TPTEP1 attenuated stemness and radioresistance of glioma both in vitro and in vivo. In addition, TPTEP1 augmented MAPK14 expression by competitively interacting with microRNA (miR)-106a-5p, thus activating the P38 MAPK signaling pathway, and suppressing glioma stemness and radioresistance. TPTEP1 functionally bound to miR-106a-5p, which formed a reciprocal regulatory loop to stimulate the P38 MAPK signaling pathway. Low TPTEP1 expression levels were detected in high-grade glioma tissues compared with low-grade glioma tissues, and were positively associated with poor prognosis of patients with glioma. Furthermore, analysis using data from The Cancer Genome Atlas database confirmed the molecular mechanism and biological significance of dysregulation of TPTEP1 in glioma progression. Taken together, the results of the present study suggest that TPTEP1 may be applied as a diagnostic and prognostic indicator for glioma, and may be an alternative target for the treatment of glioma.
- Published
- 2020