Downregulation of GPR160 inhibits the progression of glioma through suppressing epithelial to mesenchymal transition (EMT) biomarkers

Abstract

Background Glioma is one of the most fatal types of malignant tumours, the cause of which is mostly unknown. Orphan GPCRs (GPRs) have been previously implicated in tumour growth and metastasis. Therefore, these GPRs could prove to be alternative and promising therapeutic targets for cancer treatment. Objective The role of GPR160 in glioma has not yet been assessed. This study aims to explore the association of GPR160 with glioma progression and investigate its role in epithelial‐to‐mesenchymal transition (EMT) and metastasis. Methods Changes in protein expression were assessed using western blot analysis and immunofluorescent staining assays, while mRNA expression changes were evaluated using qRT‐PCR. To detect the changes in progression and metastasis, MTT, EdU proliferation, wound healing, transwell migration, and flow cytometry assays were carried out in vitro. An epithelial to mesenchymal phenotypic analysis was performed to detect EMT. Results We demonstrated that knockdown of GPR160 inhibited proliferation, colony formation, and cell viability and promoted apoptosis. Pro‐apoptotic biomarkers were upregulated, while anti‐apoptotic biomarkers were downregulated. Cell lines with GPR160 knockdown (GPR160 KD) showed a slowed migration rate and decreased invasion ability. EMT mesenchymal biomarkers were downregulated in GPR160 KD cell lines, while epithelial biomarkers were upregulated. Conclusion This study provides evidence that GPR160 is a potential therapeutic target in glioma for the first time. These findings can be used to discover in detail the molecular mechanism and pathways through which GPR160 promotes glioma progression.

A novel classifier combining G protein-coupled receptors and the tumor microenvironment is associated with survival status in glioblastoma

“…Notably, a series of adhesion GPCRs exhibit high expression levels in GBM tissues ( Stephan et al, 2021 ), which aligns with our study ( Figure 1A ). GPCR160 is upregulated in U251 and H4 glioma cell lines, and its downregulation with siRNA has led to inhibited glioma cell proliferation, reduced migration, induced apoptosis, and decreased EMT biomarkers ( Abbas et al, 2022 ). Similarly, miRNA-449a-mediated inhibition of GPCR158 suppressed glioma proliferation, particularly in high-grade glioma, while knockdown of GPCR158 increased the proliferation, migration, and sphere formation in GBM cell lines ( Li et al, 2018 ).…”

STAT3 phosphorylation inhibitor Bt354 exhibits anti‐neoplastic activity in glioblastoma multiforme cells

“…Cancer‐related deaths are frequently brought on by metastasis. Epithelial cells go through biological changes known as epithelial‐mesenchymal transition (EMT) pathway, that enables them to acquire the phenotype of stem cells and improve their migratory ability, invasive capability, and ability to withstand apoptosis 19–22 . It has been revealed that several signaling pathways, including the STAT3 pathway, contribute to the establishment of the EMT process in breast cancer 23 .…”

“…Epithelial cells go through biological changes known as epithelialmesenchymal transition (EMT) pathway, that enables them to acquire the phenotype of stem cells and improve their migratory ability, invasive capability, and ability to withstand apoptosis. [19][20][21][22] It has been revealed that several signaling pathways, including the STAT3 pathway, contribute to the establishment of the EMT process in breast cancer. 23 STAT3 upregulation in cancer-associated fibroblasts promotes angiogenesis in colorectal cancer and is linked to a poor prognosis.…”

The Role of Cocaine- and Amphetamine-Regulated Transcript (CART) in Cancer: A Systematic Review

“…In prostate cancer cells, the GPR160 knockdown increased expression of caspase 1 and interleukin 6, inhibited cell proliferation and evoked apoptosis [ 22 ]. Similarly, knockdown of GPR160 in glioma cells resulted in the promotion of apoptosis, decreased proliferation rate, reduced cell viability and diminished invasion ability [ 23 ]. In triple-negative breast cancer, GPR160 was found to be downregulated, and its higher level was correlated with better prognosis [ 24 ].…”

“…• Paraffin-embedded specimens from: gastric carcinoids (28), ileal carcinoids (58), rectal carcinoids (15), EPT (9), MTC (23).…”