Abstract
Increasing evidences show that XRCC6 (X-ray repair complementing defective repair in Chinese hamster cells 6) was upregulated and involved in tumor growth in several tumor types. However, the correlation of XRCC6 and human osteosarcoma (OS) is still unknown. This study was conducted with the aim to reveal the expression and biological function of XRCC6 in OS and elucidate the potential mechanism. The mRNA expression level of XRCC6 was measured in osteosarcoma cells and OS samples by quantitative transcription-PCR (qRT-PCR). The expression of XRCC6 protein was measured using Western blot and immunohistochemical staining in osteosarcoma cell lines and patient samples. Cell Counting Kit 8 (CCK8), colony-forming and cell cycle assays were used to test cell survival capacity. We found that XRCC6 was overexpressed in OS cells and OS samples compared with the adjacent non-tumorous samples. High expression of XRCC6 was correlated with clinical stage and tumor size in OS. Reduced expression of XRCC6 inhibits OS cell proliferation through G2/M phase arrest. Most importantly, further experiments demonstrated that XRCC6 might regulate OS growth through the β-catenin/Wnt signaling pathway. In conclusion, these findings indicate that XRCC6 exerts tumor-promoting effects for OS through β-catenin/Wnt signaling pathway. XRCC6 may serve as a novel therapeutic target for OS patients.
Highlights
The incidence of osteosarcoma (OS) ranks first among of all primary malignant bone tumors, predominantly affecting children and adolescence populations [1]
As the ββ-catenin//WWnnttssiiggnnaalilninggppaatthhwwaayywwaasswwiiddeellyyrreeppoorrtteedd iinn OOSS and correlated to tumor growth, and several ssttuuddies rreevveeaalleedd tthhaatt XXRRCCCC66 wwaassaarreegguulalattoorrooffththeeββ-c-caatetenninin//Wnt signaling pathway [20,21], we examined whether XRCC6 could inflfluence OS cell proliferation by reegulating downstream of these pathways using Western bblot aannaalysis
In this study, we provide novel evidence that XRCC6 was upregulated in OS cell lines and OS tissues
Summary
The incidence of osteosarcoma (OS) ranks first among of all primary malignant bone tumors, predominantly affecting children and adolescence populations [1]. It often occurs in long bones, such as distal femur and proximal radius [2,3]. X-ray repair complementing defective repair in Chinese hamster cells 6 (XRCC6) is a gene coding Ku70 protein [8]. It was reported to be involved in DNA recombination and repair, which plays a crucial role in genome stability and cell survival [9]. XRCC6 was reported as a key-element in the Non Homologous End Joining pathway and bound to DNA termini to protect DNA ends with high
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