Long non-coding RNA ZFAS1 sponges miR-486 to promote osteosarcoma cells progression and metastasis in vitro and vivo
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Nan Li1,*, Zhen-Hui Sun1,*, Min Fang1, Jing-Yi Xin1 and Chun-You Wan1
1Department of Traumatic Orthopedics, Tianjin Hospital, Tianjin 300211, China
*These authors have contributed equally to this work
Jing-Yi Xin, email: [email protected]
Chun-You Wa, email: [email protected]
Keywords: osteosarcoma; lncRNA; ZFAS1; miR-486; competing endogenous RNA
Received: July 22, 2017 Accepted: September 21, 2017 Published: October 24, 2017
Long noncoding RNAs (lncRNAs) have been wildly demonstrated to participate in the osteosarcoma tumorigenesis. ZFAS1 is a novel identified lncRNA, however, its role in osteosarcoma is still unclear. In present study, we utilize lncRNA microarray assay to screen the lncRNA expression profile in osteosarcoma tissue, and investigate the regulatory function of ZFAS1 in osteosarcoma. LncRNA microarray assay revealed that lncRNA ZFAS1 was significantly up-regulated in 3 pairs of osteosarcoma and adjacent non-tumor tissue, which was confirmed by RT-PCR. Furthermore, in 53 pairs of osteosarcoma patient samples, the up-regulated expression of ZFAS1 was closely related to poor prognosis. In vitro, loss-of-function experiments showed that ZFAS1 knockdown significantly suppressed the proliferation, induced cycle arrest at G0/G1 phase and enhance apoptosis. In vivo, ZFAS1 knockdown inhibited the tumor growth. Bioinformatics online programs predicted that ZFAS1 sponge miR-486 at 3’-UTR with complementary binding sites, which was validated using luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Rescue experiments confirmed that miR-486 could reverse the functions of ZFAS1 on osteosarcoma genesis. In conclusion, our results demonstrate that ZFAS1 act as competing endogenous RNA (ceRNA) for miR-486, and act as oncogene in osteosarcoma tumorigenesis, and discover the functional regulatory pathway of ZFAS1 sponging miR-486.
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