lncRNA TPTEP1 inhibits stemness and radioresistance of glioma through miR‑106a‑5p‑mediated P38 MAPK signaling

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.

Exosomal transfer of miR‐106a‐5p contributes to cisplatin resistance and tumorigenesis in nasopharyngeal carcinoma

“… 21 Another study identified that indeed miR‐106a‐5p was highly expressed and associated with a poor prognosis in triple‐negative breast cancer. 22 Studies on gastric cancer 23 and hepatocellular carcinoma 24 also confirmed that miR‐106a‐5p indeed played a vital role in tumorigenesis.…”

“… 17 Many studies have shown that the main function of miR is to control tumour progression, and one such miR is miR‐106a‐5p. 21 , 22 A study on ovarian cancer identified miR‐106a‐5p could promote tumour progression by binding and regulating the target gene ARHGAP24. 21 Another study identified that indeed miR‐106a‐5p was highly expressed and associated with a poor prognosis in triple‐negative breast cancer.…”

“…MicroRNAs (miRs) are a class of non-coding RNAs that have been identified to confer tumorigenesis. 20 These miRs are usually [20][21][22] nt in length and play a vital role in the regulation of target genes.…”

The p38 MAPK Components and Modulators as Biomarkers and Molecular Targets in Cancer

“…On the other hand, the p38 MAPK pathway has been also involved in cervical cancer through the miR-409-3p/CDK8 axis [ 49 ]. In glial tumors, a modulation of the p38 MAPK signaling pathway through miR-106a-5p suppressed glioma stemness and radioresistance [ 50 ] In pancreatic cancer, miR-27a-3p was involved in the induction of apoptosis via the modulation of p38 MAPK through the upregulation of the long noncoding RNA DGR5 [ 51 ].…”

Long non-coding RNAs in brain tumors: roles and potential as therapeutic targets

“…The transmembrane phosphatase with tensin homology pseudogene 1 (TPTEP1) lncRNA is one of the most downregulated lncRNAs in non-small cell lung cancer, where it inhibits the cell proliferation by competitively sponging miR-328-5p [ 58 ]. In glioma, TPTEP1 promotes the P38 MAPK pathway through competitive interactions with miR-106a-5p, thus inhibiting stemness and radioresistance [ 59 ].…”