The PODNL1/AKT/β-catenin signaling axis mediates glioma progression and sensitivity to temozolomide
Abnormal expression of small leucine-rich repeat proteins (SLRP) in tumor tissues has been reported as a critical trigger for tumorigenesis and progression. However, the molecular mechanism of PODNL1, a novel member of SLRP family, in glioma remains largely unknown. Therefore, this study aimed to in...
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KeAi Communications Co. Ltd.
2025-07-01
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| Series: | Fundamental Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667325823000869 |
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| author | Shanqiang Qu Chengying Huang Zhicheng Hu |
| author_facet | Shanqiang Qu Chengying Huang Zhicheng Hu |
| author_sort | Shanqiang Qu |
| collection | DOAJ |
| description | Abnormal expression of small leucine-rich repeat proteins (SLRP) in tumor tissues has been reported as a critical trigger for tumorigenesis and progression. However, the molecular mechanism of PODNL1, a novel member of SLRP family, in glioma remains largely unknown. Therefore, this study aimed to investigate its correlation with clinical factors by glioma cohort and to identify the molecular mechanisms of aberrant PODNL1 gene expression in glioma. Our findings revealed that both PODNL1 mRNA and protein levels were markedly upregulated in glioma tissues, and high PODNL1 mRNA level was significantly associated with poor prognosis of glioma patients. In functional assays, PODNL1 knockdown significantly suppressed the proliferation and invasion abilities of glioma cells, while overexpression of PODNL1 had the opposite effect both in vitro and in vivo. Mechanistically, PODNL1 knockdown suppressed the activation of AKT/mTOR signaling and inhibited nuclear translocation of β-catenin protein in the glioma cells. Our results suggest that PODNL1 acts as an oncogenic factor in glioma by promoting glioma progression through the activation of the kinase AKT, which indeces β-catenin nuclear translocation. Additionally, PODNL1 knockdown enhanced the sensitivity of glioma cells to temozolomide, a chemotherapeutic agent commonly used in the treatment of glioma. The PODNL1/AKT/β-catenin signaling axis represents a new potential therapeutic target against glioma. Furthermore, our data showed the combination of temozolomide and MK-2206, an AKT inhibitor, had a synergistic antitumor effect against glioma cells. |
| format | Article |
| id | doaj-art-f5e249838b1140d4b9655c1c582211d8 |
| institution | Kabale University |
| issn | 2667-3258 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | KeAi Communications Co. Ltd. |
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| series | Fundamental Research |
| spelling | doaj-art-f5e249838b1140d4b9655c1c582211d82025-08-20T03:56:50ZengKeAi Communications Co. Ltd.Fundamental Research2667-32582025-07-01541822183010.1016/j.fmre.2023.03.005The PODNL1/AKT/β-catenin signaling axis mediates glioma progression and sensitivity to temozolomideShanqiang Qu0Chengying Huang1Zhicheng Hu2Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; The Laboratory for Precision Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Corresponding authors.Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou 510080, ChinaDepartment of Burn surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Corresponding authors.Abnormal expression of small leucine-rich repeat proteins (SLRP) in tumor tissues has been reported as a critical trigger for tumorigenesis and progression. However, the molecular mechanism of PODNL1, a novel member of SLRP family, in glioma remains largely unknown. Therefore, this study aimed to investigate its correlation with clinical factors by glioma cohort and to identify the molecular mechanisms of aberrant PODNL1 gene expression in glioma. Our findings revealed that both PODNL1 mRNA and protein levels were markedly upregulated in glioma tissues, and high PODNL1 mRNA level was significantly associated with poor prognosis of glioma patients. In functional assays, PODNL1 knockdown significantly suppressed the proliferation and invasion abilities of glioma cells, while overexpression of PODNL1 had the opposite effect both in vitro and in vivo. Mechanistically, PODNL1 knockdown suppressed the activation of AKT/mTOR signaling and inhibited nuclear translocation of β-catenin protein in the glioma cells. Our results suggest that PODNL1 acts as an oncogenic factor in glioma by promoting glioma progression through the activation of the kinase AKT, which indeces β-catenin nuclear translocation. Additionally, PODNL1 knockdown enhanced the sensitivity of glioma cells to temozolomide, a chemotherapeutic agent commonly used in the treatment of glioma. The PODNL1/AKT/β-catenin signaling axis represents a new potential therapeutic target against glioma. Furthermore, our data showed the combination of temozolomide and MK-2206, an AKT inhibitor, had a synergistic antitumor effect against glioma cells.http://www.sciencedirect.com/science/article/pii/S2667325823000869GliomaBiomarkerTherapyMalignant phenotypePODNL1 |
| spellingShingle | Shanqiang Qu Chengying Huang Zhicheng Hu The PODNL1/AKT/β-catenin signaling axis mediates glioma progression and sensitivity to temozolomide Fundamental Research Glioma Biomarker Therapy Malignant phenotype PODNL1 |
| title | The PODNL1/AKT/β-catenin signaling axis mediates glioma progression and sensitivity to temozolomide |
| title_full | The PODNL1/AKT/β-catenin signaling axis mediates glioma progression and sensitivity to temozolomide |
| title_fullStr | The PODNL1/AKT/β-catenin signaling axis mediates glioma progression and sensitivity to temozolomide |
| title_full_unstemmed | The PODNL1/AKT/β-catenin signaling axis mediates glioma progression and sensitivity to temozolomide |
| title_short | The PODNL1/AKT/β-catenin signaling axis mediates glioma progression and sensitivity to temozolomide |
| title_sort | podnl1 akt β catenin signaling axis mediates glioma progression and sensitivity to temozolomide |
| topic | Glioma Biomarker Therapy Malignant phenotype PODNL1 |
| url | http://www.sciencedirect.com/science/article/pii/S2667325823000869 |
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