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ZIC2 promotes viability and invasion of human osteosarcoma cells by suppressing SHIP2 expression and activating
1Department of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Abstract:
Osteosarcoma is a malignant tumor of the skeletal system. The zinc finger transcription factor ZIC2 has been reported to be highly expressed in human cancers. The present study evaluated the effects of ZIC2 and the possible underlying mechanisms in the human osteosarcoma cells. The expression levels of ZIC2 in human fetal osteoblastic cell line (hFOB1.19), osteosarcoma cell lines (U-2OS, SaoS2, and MG63), normal bone tissue, and osteosarcoma tumor were analyzed by Western blot, and real-time quantitative RT-PCR (qRT-PCR). Osteosarcoma cells with either overexpressed ZIC2 or suppressed ZIC2 were analyzed to determine cell viability, colony formation, and cell invasion. The expressions of SHIP2 and PI3K/AKT signal pathway-related proteins were analyzed by Western blot and qRT-PCR. We first showed that ZIC2 is highly expressed in osteosarcoma cells and tissues. Then we demonstrated that overexpression of ZIC2 promoted viability, migration, and invasion of osteosarcoma cells, whereas suppression of ZIC2 showed opposite effects. Furthermore, SHIP2 expression was negatively regulated by ZIC2. Importantly, ZIC2 overexpression activated the PI3K/AKT signal pathway; however, overexpressed SHIP2 inhibited these effects. Lastly, we showed that activation of the PI3K/AKT signal pathway is essential for the effects of ZIC2 on osteosarcoma cells, as the effects of ZIC2 on the osteosarcoma cells were reversed by a PI3K/AKT inhibitor. Overall, ZIC2 is highly expressed in osteosarcoma cells and tissues, and its overexpression promotes viability, invasion of osteosarcoma cells via SHIP2 suppression, and PI3K/AKT activation. Thus, ZIC2 can be considered as a novel drug target for osteosarcoma management.
Insights
The zinc finger transcription factor ZIC2 is highly expressed in osteosarcoma, promoting cancer cell viability and invasion. Suppressing ZIC2 or activating the PI3K/AKT pathway offers potential therapeutic strategies for osteosarcoma management.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma is a primary malignant bone tumor.
- The zinc finger transcription factor ZIC2 is implicated in various human cancers.
- Understanding ZIC2's role in osteosarcoma is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the expression levels of ZIC2 in osteosarcoma.
- To elucidate the functional effects of ZIC2 on osteosarcoma cell behavior.
- To explore the underlying molecular mechanisms involving SHIP2 and the PI3K/AKT pathway.
Main Methods:
- Western blot and real-time quantitative RT-PCR (qRT-PCR) for analyzing protein and gene expression.
- Functional assays to assess cell viability, colony formation, and invasion.
- Manipulation of ZIC2 and SHIP2 expression levels in osteosarcoma cell lines.
- Pharmacological inhibition of the PI3K/AKT signaling pathway.
Main Results:
- ZIC2 expression is significantly elevated in osteosarcoma cells and tissues compared to normal controls.
- Overexpression of ZIC2 enhances osteosarcoma cell viability, migration, and invasion.
- ZIC2 negatively regulates SHIP2 expression and activates the PI3K/AKT signaling pathway.
- Inhibition of PI3K/AKT signaling reverses the pro-tumorigenic effects of ZIC2.
Conclusions:
- ZIC2 is a key driver of osteosarcoma progression.
- ZIC2 promotes osteosarcoma cell viability and invasion by suppressing SHIP2 and activating the PI3K/AKT pathway.
- ZIC2 represents a promising therapeutic target for osteosarcoma treatment.
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