Long Noncoding RNA LINC00909 Induces Epithelial-Mesenchymal Transition and Contributes to Osteosarcoma Tumorigenesis and Metastasis

Wanshun Liu; Qi Zhang; Kai Shen; Keran Li; Jie Chang; He Li; Ao Duan; Sheng Zhang; Yumin Huang

doi:10.1155/2022/8660965

Long Noncoding RNA LINC00909 Induces Epithelial-Mesenchymal Transition and Contributes to Osteosarcoma Tumorigenesis and Metastasis

J Oncol. 2022 Oct 10:2022:8660965. doi: 10.1155/2022/8660965. eCollection 2022.

Authors

Wanshun Liu^{1

2}, Qi Zhang³, Kai Shen¹, Keran Li⁴, Jie Chang¹, He Li¹, Ao Duan¹, Sheng Zhang^{1

5}, Yumin Huang¹

Affiliations

¹ Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road Nanjing, 210029 Jiangsu, China.
² Department of Orthopedics, Nanjing First Hospital of Nanjing Medical University, Nanjing 210006, China.
³ Department of Pain Management, Sir Run Run Hospital, Nanjing Medical University, Nanjing 211100, China.
⁴ Department of Cataract, The Affiliated Eye Hospital of Nanjing Medical University, 138 Hanzhong Road, Nanjing, 210003 Jiangsu, China.
⁵ Department of Orthopedics, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, 210009 Jiangsu, China.

Abstract

Background: Osteosarcoma (OS) is a malignant tumor that is highly metastatic with a high mortality rate. Although mounting evidence suggests that LINC00909 is strongly associated with the malignant progression of various tumors, the exact role of LINC00909 in OS remains unknown. Therefore, the current study was designed to investigate the relationship between LINC00909 and the malignant progression of OS.

Methods: LINC00909 expression was measured in OS cell lines and clinical specimens using RT-qPCR assays. The effects of LINC00909 on OS proliferation, invasion, and migration were calculated both in vitro and in vivo. Apart from that, bioinformatics analyses, FISH, RIP, and luciferase reporter assays were carried out to investigate the downstream target of LINC00909. Rescue experiments were also conducted to investigate the potential mechanisms of action of competitive endogenous RNAs (ceRNAs).

Results: In this study, we found that LINC00909 was highly expressed in OS cell lines and clinical specimens. In vivo and in vitro experiments demonstrated that LINC00909 induces epithelial-to-mesenchymal transition (EMT) and contributes to OS tumorigenesis and metastasis. FISH, RIP, and luciferase assays indicated that miR-875-5p is a direct target of LINC00909. Moreover, HOXD9 was validated as the downstream target of miR-875-5p in a luciferase reporter assay and western blotting experiments. Rescue experiments revealed that HOXD9 reversed the effect of LV-sh-LINC00909 on OS cells by positively regulating the PI3K/AKT/mTOR signaling pathway.

Conclusion: Collectively, LINC00909 induces EMT and contributes to OS tumorigenesis and metastasis through the PI3K/AKT/mTOR pathway by binding to miR-875-5p to upregulate HOXD9 expression. Targeting the LINC00909/miR-875-5p/HOXD9 axis may have potential in treating OS.