2. Academic Validation
  3. Transcription factor CREB1 promotes malignant growth of osteosarcoma cells by inhibiting miRNA-183-5p and regulating PROX1 expression

Transcription factor CREB1 promotes malignant growth of osteosarcoma cells by inhibiting miRNA-183-5p and regulating PROX1 expression

  • Mol Biol Rep. 2025 Jun 28;52(1):647. doi: 10.1007/s11033-025-10741-7.
Fei Jin 1,  Kaibing Long 2,  Jian Zhang 3
Affiliations

Affiliations

  • 1 Department of Orthopedics, Hunan Aerospace Hospital, No. 189, Fenglin Third Road, Yuelu District, Changsha, 410205, Hunan, China. 956291725@qq.com.
  • 2 Department of Orthopedics, Hunan Aerospace Hospital, No. 189, Fenglin Third Road, Yuelu District, Changsha, 410205, Hunan, China.
  • 3 Department of Orthopedics, The First Affiliated Hospital of University of South China, Hengyang, Hunan, China.
PMID: 40579642 DOI: 10.1007/s11033-025-10741-7
Abstract

Background: Osteosarcoma is a malignant tumor in bone and soft tissue tumors, characterized by high invasiveness and low survival rate. Here, we studied the effect of cAMP-responsive element binding protein 1 (CREB1) on osteosarcoma cell proliferation and invasion.

Methods: mRNA levels of CREB1, miRNA-183-5p and prospero homeobox 1 (PROX1) were detected by quantitative real-time polymerase chain reaction (RT-qPCR), while CREB1 and PROX1 protein levels were evaluated utilizing Western blot in osteosarcoma cell lines and tissues. Immunohistochemistry investigated CREB1 expression in osteosarcoma tissues. Colony formation, transwell and flow cytometry experiments detected cell proliferation, invasion and Apoptosis, respectively. Dual luciferase reporter assay, chromatin immunoprecipitation (ChIP) assay and RNA immunoprecipitation (RIP) assay verified target relationship between CREB1, miRNA-183-5p and PROX1.

Results: CREB1 expression was increased in osteosarcoma tissues and cells. Reduced CREB1 inhibited osteosarcoma cell proliferation and invasion, and promoted Apoptosis. Moreover, CREB1 targets miRNA-183-5p and transcriptionally inhibited miRNA-183-5p expression in osteosarcoma cells. Additionally, PROX1 was a target gene of miRNA-183-5p, where expression was inhibited by miRNA-183-5p. PROX1 upregulation reversed inhibitory effect of miRNA-183-5p overexpression on osteosarcoma cell malignant phenotype.

Conclusion: Downregulation of CREB1 inhibited osteosarcoma cell proliferation and invasion but induced Apoptosis through miRNA-183-5p/PROX1 axis. CREB1 may become a new target for diagnosis and treatment of osteosarcoma.

Keywords

CREB1; Osteosarcoma; PROX1; miRNA-183-5p.

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