A Feedback Loop of LINC00665 and the Wnt Signaling Pathway Expedites Osteosarcoma Cell Proliferation, Invasion, and Epithelial-Mesenchymal Transition

Orthopaedic Surgery, 2023 · DOI: 10.1111/os.13532 · Published: January 1, 2023

Simple Explanation

This study explores the role of a long non-coding RNA called LINC00665 in osteosarcoma (OS), a type of bone cancer common in teenagers. The study found that LINC00665 is present at higher levels in OS cells and promotes their growth and spread. The researchers discovered that LINC00665 interacts with a molecule called miR-1249-5p, which in turn affects the Wnt signaling pathway, a critical regulator of cell development and growth. This interaction forms a feedback loop that accelerates cancer cell proliferation, invasion, and a process called epithelial-mesenchymal transition (EMT). The findings suggest that targeting this LINC00665/miR-1249-5p/WNT2B/Wnt pathway could be a potential strategy for treating OS, offering a new avenue for developing effective biomarkers and therapies.

Study Duration

Not specified

Participants

Four Osteosarcoma cell lines (U2OS, SAOS-2, MG-63, 143B) and human fetal osteoblasts (hFOB)

Evidence Level

Not specified

Key Findings

1
LINC00665 is significantly upregulated in OS cells compared to normal bone cells, suggesting its involvement in OS development.
2
Silencing LINC00665 inhibits OS cell proliferation, migration, invasion, and EMT, while promoting cell apoptosis, indicating its cancer-promoting role.
3
LINC00665 acts as a ceRNA (competing endogenous RNA) to sponge miR-1249-5p, thereby modulating WNT2B expression and activating the Wnt pathway.

Research Summary

This study investigates the role of LINC00665 in osteosarcoma (OS) cells, revealing its significant up-regulation and cancer-promoting function. It demonstrates that LINC00665 promotes OS cell proliferation, migration, invasion, and EMT while repressing cell apoptosis. Mechanistically, LINC00665 functions as a ceRNA to sponge miR-1249-5p, leading to the modulation of WNT2B expression and activation of the Wnt pathway. Furthermore, the Wnt pathway transcriptionally activates LINC00665 expression, forming a positive feedback loop. The study concludes that the LINC00665/miR-1249-5p/WNT2B/Wnt feedback loop plays a crucial role in OS progression, suggesting LINC00665 as a potential therapeutic target. These findings imply that LINC00665 might serve as a novel biomarker in OS treatment.

Practical Implications

Therapeutic Target

The LINC00665/miR-1249-5p/WNT2B/Wnt pathway could be a potential therapeutic target for osteosarcoma treatment.

Biomarker Potential

LINC00665 may serve as a novel biomarker for osteosarcoma diagnosis and prognosis.

Drug Development

Targeting LINC00665 could lead to the development of new drugs to combat osteosarcoma progression.

Study Limitations

1
The study lacks clinical sample validation to confirm LINC00665 expression in osteosarcoma patients.
2
Xenograft models are needed to analyze the validity of the LINC00665/miR-1249-5p/WNT2B/Wnt loop in vivo.
3
Further research is needed to fully elucidate the downstream targets and signaling pathways regulated by the LINC00665/miR-1249-5p/WNT2B/Wnt axis.

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