Reduced PTCH2 expression is associated with glioma development through its regulation of the PTEN/AKT signaling
Jizhong Han1, Huajiang Deng1, Yu Xiong1
1Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China; Sichuan Clinical Research Center for Neurosurgery, Luzhou, 646000, China; Laboratory of Neurological Disease and Brain Function, Luzhou, 646000, China.
Abstract:
Mutations in the human protein patched homolog (PTCH) gene have been demonstrated to be associated with cancer development in several types of malignancy. However, the underlying mechanism of PTCH-associated cancer development remains poorly understood, to the best of our knowledge. In the present study, the expression of PTCH2 in glioma tumor tissues from The Cancer Genome Atlas (TCGA) database and clinical patients with glioma were measured. Reduced expression levels of PTCH2 were observed in patients with glioma with poor prognose. In vitro, overexpression of PTCH2 significantly suppressed the proliferation and invasion of the glioma cell lines, LN229 and U87-MG. Mechanistically, PTCH2 upregulated the expression of tumor suppressor PTEN, thereby leading to the suppression of pro-survival AKT signals in glioma. Reduced expression of PTEN and enhanced expression of AKT promoted glioma development in vitro and in vivo. Blockade of PTCH2/AKT signals efficiently strengthened the anticancer effects of chemotherapy and prolonged the survival time in tumor-bearing mice, which provided a novel insight into potential treatment strategies for glioma in the clinic.
Insights
Reduced PTCH2 expression correlates with poor glioma prognosis. Restoring PTCH2 suppresses glioma growth by upregulating PTEN and inhibiting AKT, offering new therapeutic strategies for brain tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Mutations in the human protein patched homolog (PTCH) gene are linked to various cancers.
- The specific role of PTCH2 in glioma development and its underlying mechanisms are not well understood.
Purpose of the Study:
- To investigate the expression and function of PTCH2 in glioma.
- To elucidate the molecular mechanisms by which PTCH2 influences glioma progression.
- To explore PTCH2 as a potential therapeutic target for glioma.
Main Methods:
- Analysis of PTCH2 expression in The Cancer Genome Atlas (TCGA) database and clinical glioma samples.
- In vitro experiments involving overexpression of PTCH2 in glioma cell lines (LN229, U87-MG).
- Investigation of the PTCH2/PTEN/AKT signaling pathway.
- In vivo studies using tumor-bearing mice to assess therapeutic strategies.
Main Results:
- Lower PTCH2 expression was observed in glioma patients with poor prognoses.
- Overexpression of PTCH2 inhibited glioma cell proliferation and invasion.
- PTCH2 was found to upregulate tumor suppressor PTEN, subsequently suppressing pro-survival AKT signaling.
- Reduced PTEN and elevated AKT expression promoted glioma development in vitro and in vivo.
- Blocking PTCH2/AKT signaling enhanced chemotherapy efficacy and prolonged survival in mice.
Conclusions:
- PTCH2 acts as a tumor suppressor in glioma by regulating the PTEN/AKT pathway.
- PTCH2 expression levels are a potential prognostic biomarker for glioma.
- Targeting the PTCH2/AKT signaling axis presents a promising therapeutic strategy for glioma treatment.
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