BECN1/CAV-1 axis regulates neuronal function in the microenvironment of osteosarcoma through ERK/CREB signaling.
- 1Department of Anesthesiology, Nantong First People's Hospital, Southeast University, Nantong, China.
Abstract
Osteosarcoma progression is closely regulated by the tumor microenvironment (TME), however, the molecular mechanism remains unclear. This study aimed to explore the effects of the Beclin 1/Caveolin-1 (BECN1/CAV-1) axis on the proliferation and apoptosis of neuronal cells co-cultured with osteosarcoma cells in the TME. A bioinformatics analysis of data from the Gene Expression Omnibus (GEO) database was performed to identify differentially expressed genes (DEGs) between osteosarcoma tissues and adjacent normal tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to examine biological functions associated with the DEGs. CAV-1 expression in osteosarcoma tissues and adjacent normal tissues was then analyzed. Next, osteosarcoma cells were co-cultured with neuronal cells, and CAV-1 expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR). A small interfering RNA (siRNA) interference model was then established. Nerve cell proliferation neuronal cells was examined using the 5-ethynyl-2'-deoxyuridine (EdU) assay, while nerve cell apoptosis neuronal cells was assessed by flow cytometry. Further, changes in CAV-1 expression following siRNA transfection were analyzed by immunofluorescence assay. The expression levels of CAV-1, CREB, p-CREB, ERK1/2, and p-ERK1/2 were examined by Western blotting (WB). The interaction between CAV-1 and BECN1 was investigated by co-immunoprecipitation (Co-IP). Finally, the cells were divided into control, CAV-1, and siRNA-CAV-1 + BECN1 overexpression (OE) groups. Cell proliferation, apoptosis, and the expression levels of molecules in the ERK/CREB pathway were subsequently examined. CAV-1 expression was significantly increased in osteosarcoma tissues. CAV-1 knockdown suppressed bone cancer cell proliferation and promoted apoptosis, while also decreasing the protein expression levels of CAV-1, p-CREB and p-ERK1/2. BECN1 was overexpressed in osteosarcoma, and BECN1 may regulate the transcription of CAV-1. BECN1 OE partially reversed the effects of CAV-1 knockdown on cell proliferation, apoptosis, and CAV-1, p-CREB, and p-ERK1/2 expression. BECN1 regulates CAV-1 through the ERK/CREB pathway, thereby promoting the proliferation of co-cultured neuronal cells and inhibiting their apoptosis in the osteosarcoma microenvironment.
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BibTeX
@article{ge2026becn1cav1,
title = {{BECN1/CAV-1 axis regulates neuronal function in the microenvironment of osteosarcoma through ERK/CREB signaling.}},
author = {Jianyun Ge and Tianyu Gu and Mengmeng Cai and Xu Liu and Xin Sun and Qian Su and Jie Song},
journal = {Translational cancer research},
year = {2026},
month = oct,
doi = {10.21037/tcr-2026-1850},
url = {https://europepmc.org/article/MED/42997732},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - BECN1/CAV-1 axis regulates neuronal function in the microenvironment of osteosarcoma through ERK/CREB signaling.
AU - Jianyun Ge
AU - Tianyu Gu
AU - Mengmeng Cai
AU - Xu Liu
AU - Xin Sun
AU - Qian Su
AU - Jie Song
PY - 2026
DA - 2026/10/26
JO - Translational cancer research
DO - 10.21037/tcr-2026-1850
UR - https://europepmc.org/article/MED/42997732
AB - Osteosarcoma progression is closely regulated by the tumor microenvironment (TME), however, the molecular mechanism remains unclear. This study aimed to explore the effects of the Beclin 1/Caveolin-1 (BECN1/CAV-1) axis on the proliferation and apoptosis of neuronal cells co-cultured with osteosarcoma cells in the TME. A bioinformatics analysis of data from the Gene Expression Omnibus (GEO) database was performed to identify differentially expressed genes (DEGs) between osteosarcoma tissues and adjacent normal tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to examine biological functions associated with the DEGs. CAV-1 expression in osteosarcoma tissues and adjacent normal tissues was then analyzed. Next, osteosarcoma cells were co-cultured with neuronal cells, and CAV-1 expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR). A small interfering RNA (siRNA) interference model was then established. Nerve cell proliferation neuronal cells was examined using the 5-ethynyl-2'-deoxyuridine (EdU) assay, while nerve cell apoptosis neuronal cells was assessed by flow cytometry. Further, changes in CAV-1 expression following siRNA transfection were analyzed by immunofluorescence assay. The expression levels of CAV-1, CREB, p-CREB, ERK1/2, and p-ERK1/2 were examined by Western blotting (WB). The interaction between CAV-1 and BECN1 was investigated by co-immunoprecipitation (Co-IP). Finally, the cells were divided into control, CAV-1, and siRNA-CAV-1 + BECN1 overexpression (OE) groups. Cell proliferation, apoptosis, and the expression levels of molecules in the ERK/CREB pathway were subsequently examined. CAV-1 expression was significantly increased in osteosarcoma tissues. CAV-1 knockdown suppressed bone cancer cell proliferation and promoted apoptosis, while also decreasing the protein expression levels of CAV-1, p-CREB and p-ERK1/2. BECN1 was overexpressed in osteosarcoma, and BECN1 may regulate the transcription of CAV-1. BECN1 OE partially reversed the effects of CAV-1 knockdown on cell proliferation, apoptosis, and CAV-1, p-CREB, and p-ERK1/2 expression. BECN1 regulates CAV-1 through the ERK/CREB pathway, thereby promoting the proliferation of co-cultured neuronal cells and inhibiting their apoptosis in the osteosarcoma microenvironment.
SN - 2218-676X
SN - 2219-6803
ER -