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Int J Biol Sci 2023; 19(2):412-425. doi:10.7150/ijbs.77688 This issue Cite

Research Paper

Apelin promotes osteosarcoma metastasis by upregulating PLOD2 expression via the Hippo signaling pathway and hsa_circ_0000004/miR-1303 axis

Nguyen Thi Nha Trang1,2#, Chao-Yang Lai2#, Hsiao-Chi Tsai1, Yuan-Li Huang2,3, Shan-Chi Liu4, Chun-Hao Tsai5,6, Yi-Chin Fong5,7, Huey-En Tzeng8,9,10✉, Chih-Hsin Tang1,2,11,12✉

1. School of Medicine, China Medical University, Taichung, Taiwan.
2. Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan.
3. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
4. Department of Medical Education and Research, China Medical University Beigang Hospital, Yunlin, Taiwan.
5. Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.
6. Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan.
7. Department of Orthopaedic Surgery, China Medical University Beigang Hospital, Yunlin, Taiwan.
8. Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
9. Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
10. Ph.D. Program for Cancer Molecular Biology and Drug Discovery, and Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
11. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
12. Chinese Medicine Research Center, China Medical University, Taichung, Taiwan.
#Equal contributions to this work.

✉ Corresponding authors: Chih-Hsin Tang, PhD, Department of Pharmacology, School of Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan. Tel: (886) 4-22052121 Ext. 7726; Fax: (886) 4-22333641; E-mail: chtangcmu.ed More

Citation:
Trang NTN, Lai CY, Tsai HC, Huang YL, Liu SC, Tsai CH, Fong YC, Tzeng HE, Tang CH. Apelin promotes osteosarcoma metastasis by upregulating PLOD2 expression via the Hippo signaling pathway and hsa_circ_0000004/miR-1303 axis. Int J Biol Sci 2023; 19(2):412-425. doi:10.7150/ijbs.77688. https://www.ijbs.com/v19p0412.htm
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Abstract

Graphic abstract

Osteosarcoma is a highly mortal bone tumor, with a high metastatic potential, promoted in part by the enzyme procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2). Increasing level of PLOD2 in osteosarcoma tissue correlates with lymphatic and distant metastasis. The adipokine apelin (APLN) is also found in different cancers and APLN upregulation promotes angiogenesis and metastasis, but its effects on osteosarcoma metastasis are uncertain. We explored APLN functioning in metastatic osteosarcoma. An analysis of records from the Gene Expression Omnibus (GEO) database showed higher levels of APLN expression in osteosarcoma tissue than in normal tissue. Similarly, levels of APLN and PLOD2 mRNA synthesis were upregulated in osteosarcoma tissue. Levels of APLN and PLOD2 protein correlated positively with osteosarcoma clinical stages. APLN increased PLOD2 expression in human osteosarcoma cell lines and cell migration via the mammalian Sterile 20-like kinase 1 (MST1), monopolar spindle-one-binder protein (MOB)1, and YAP cascades, and through hsa_circ_0000004 functioning as a sponge of miR-1303. We also found that knockdown of APLN antagonized lung metastasis in mice with osteosarcoma. APLN may be a therapeutic target in osteosarcoma metastasis.

Keywords: Apelin, PLOD2, metastasis, osteosarcoma

Citation styles

APA
Trang, N.T.N., Lai, C.Y., Tsai, H.C., Huang, Y.L., Liu, S.C., Tsai, C.H., Fong, Y.C., Tzeng, H.E., Tang, C.H. (2023). Apelin promotes osteosarcoma metastasis by upregulating PLOD2 expression via the Hippo signaling pathway and hsa_circ_0000004/miR-1303 axis. International Journal of Biological Sciences, 19(2), 412-425. https://doi.org/10.7150/ijbs.77688.

ACS
Trang, N.T.N.; Lai, C.Y.; Tsai, H.C.; Huang, Y.L.; Liu, S.C.; Tsai, C.H.; Fong, Y.C.; Tzeng, H.E.; Tang, C.H. Apelin promotes osteosarcoma metastasis by upregulating PLOD2 expression via the Hippo signaling pathway and hsa_circ_0000004/miR-1303 axis. Int. J. Biol. Sci. 2023, 19 (2), 412-425. DOI: 10.7150/ijbs.77688.

NLM
Trang NTN, Lai CY, Tsai HC, Huang YL, Liu SC, Tsai CH, Fong YC, Tzeng HE, Tang CH. Apelin promotes osteosarcoma metastasis by upregulating PLOD2 expression via the Hippo signaling pathway and hsa_circ_0000004/miR-1303 axis. Int J Biol Sci 2023; 19(2):412-425. doi:10.7150/ijbs.77688. https://www.ijbs.com/v19p0412.htm

CSE
Trang NTN, Lai CY, Tsai HC, Huang YL, Liu SC, Tsai CH, Fong YC, Tzeng HE, Tang CH. 2023. Apelin promotes osteosarcoma metastasis by upregulating PLOD2 expression via the Hippo signaling pathway and hsa_circ_0000004/miR-1303 axis. Int J Biol Sci. 19(2):412-425.

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