LINC00511 Promotes Osteosarcoma Tumorigenesis and Invasiveness through the miR-185-3p/E2F1 Axis

Author:

Xu Jun1,Chen Guangnan1,Zhang Yiming1,Huang Zhongyue1,Cheng Xiangyang1,Gu Huijie1,Xia Jiangni1ORCID,Yin Xiaofan1ORCID

Affiliation:

1. Department of Orthopaedics, Minhang Hospital, Fudan University, 170 Xin-Song Road, Shanghai 201199, China

Abstract

Osteosarcoma is a malignant tumor that seriously threatens human health. Numerous studies have pointed out the potential of long noncoding RNAs (lncRNAs) as new therapeutic targets for various human cancers. Therefore, we mainly investigate whether there is a new type of lncRNA pathway involved in regulating the development of osteosarcoma. The present study shows the higher expression levels of LINC00511 correlates to a shorter overall survival and disease-free survival time in patients with sarcoma. It is significantly higher in the clinical samples of osteosarcoma patients than in normal adjacent cancer tissues. We used U373 and SW1353 osteosarcoma cells to determine the effect of lncRNA on osteosarcoma proliferation and invasion by knocking down LINC00511 compared with controls. The results showed that the LINC00511 knockdown significantly suppressed osteosarcoma cell growth and metastasis. To explore the mechanisms of LINC00511 in osteosarcoma, we tested whether LINC00511 could competitively stimulate miR-185-3p and regulate E2F1 as a ceRNA. The results showed that LINC00511 knockdown induced the increased level of miR-185-3p levels; however, miR-185-3p overexpression suppressed LINC00511 levels. In addition, the results also demonstrated that LINC00511 knockdown or miR-185-3p overexpression could reduce E2F1 levels in osteosarcoma cells. The dual-luciferase reporter assay verified the direct interaction between miR-185-3p and LINC00511 or E2F1. These results may offer an explanation of how the lncRNA affects the progression of osteosarcoma, and our study shows that LINC00511 can be a novel biomarker in osteosarcoma.

Funder

National Natural Science Foundation of China

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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