Abstract
Lung is the primary site of osteosarcoma metastasis, but the underlying genetic or epigenetic factors determining lung metastasis of osteosarcoma are unknown. In this study, we report the status of growth arrest specific 5 (GAS5) in lung metastatic osteosarcomas. GAS5 was generally downregulated in osteosarcoma patients (n = 24) compared to healthy controls (n = 10) and even more so in patients with lung metastatic disease(n = 11) compared to the patients without metastasis (n = 13). We also report a role of miR-21 in GAS5-mediated effects. Downregulation of GAS5 in hFOB 1.19 and U2OS osteosarcoma cells enhanced their migration and invasion, along with an upregulated epithelial–mesenchymal transition (EMT), as evidenced by downregulated E-cadherin and upregulated vimentin, ZEB1, and ZEB2. Downregulation of GAS5 also resulted in a significantly increased expression of miR-21. Moreover, downregulation of such elevated miR-21 was found to reverse the effects of GAS5 silencing. miR-21 was also found to be elevated in osteosarcoma patients with its levels particularly high in patients with lung metastasis. Our observations reveal a possible role of GAS5 and miR-21 in lung metastasis of osteosarcoma, presenting them as novel targets for therapy.
Highlights
Osteosarcoma is a type of bone cancer diagnosed in young adults and teenagers more frequently than at a later stage (Wittig et al, 2002)
We first evaluated the levels of growth arrest specific 5 (GAS5), by quantitative realtime PCR, in osteosarcoma patients (n = 24) and compared the levels of GAS5 in patients with those in the archived samples from healthy controls (n = 10)
Our analysis revealed that compared to controls, GAS5 was significantly downregulated even in the osteosarcoma patients without metastasis (Figure 1A) (p < 0.05)
Summary
Osteosarcoma is a type of bone cancer diagnosed in young adults and teenagers more frequently than at a later stage (Wittig et al, 2002). It is more common in long bones such as those in the legs (Ferguson and Turner, 2018) but can be diagnosed in any bone. Lungs are one of the most common sites of cancer metastasis (Jamil and Kasi, 2021) including from osteosarcomas (Saha et al, 2013), and the mechanisms and underlying causes of lung metastases of primary osteosarcomas largely remain unknown. The 5-year survival rates of osteosarcoma patients with lung metastatic disease are quite dismal (Farfalli et al, 2015), and there is an urgent need to better understand the genetic or the epigenetic factors that can regulate lung metastasis of osteosarcomas
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
