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.
Highlights
Osteosarcoma is a highly malignant tumor with a low incidence, mainly in adolescents, and it is one of the major cancers causing death in childhood [1]
Our experimental results indicated that LINC00511 was a higher expression in osteosarcoma cells
In-depth research found that LINC00511 promoted the development of osteosarcoma cells by regulating the miR185-3p/E2F1 axis
Summary
Osteosarcoma is a highly malignant tumor with a low incidence, mainly in adolescents, and it is one of the major cancers causing death in childhood [1]. The continuous discovery of small molecules has led to an increasing number of studies on them, especially their functions and mechanisms in the development of cancer [5]. Studies have found that lncRNAs are differentially expressed in cancer tissues and adjacent tissues, which is very interesting, suggesting that lncRNAs participates in the development of cancer cells [6]. The molecular intervention in the development of tumor cells has been a new strategy for the treatment of cancer [7, 8]. In lung cancer, lncRNA HOX transcriptional antisense RNA (HOTAIR) in tumor tissues is higher than that in adjacent nontumor tissues [9]. HOTAIR can inhibit the expression of p21WAF1/CIP1 genes and promote the proliferation, metastasis, invasion, and drug resistance of lung cancer cells [10]. In the patients with colorectal cancer (CRC) stage II/III, the level of lncRNA MALAT1 in cancer tissues is higher than
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