Anti-E2F1 monoclonal antibody, clone JG96

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.

SLC47A2 encodes MATE 2-K in the kidney, which mediates the secretion of certain endogenous and exogenous compounds. SLC47A2 was dramatically repressed in patients with renal cell carcinoma (RCC), and a lower level of SLC47A2 might act as a negative prognostic marker, although the mechanism is not well understood. In this study, we aimed to investigate the mechanism via which SLC47A2 is downregulated in RCC. Based on the annotation information of the SLC47A2 locus available in the UCSC genome browser database, we identified a novel lncRNA, which is transcribed from the SLC47A2 locus and named it SANT1. Overexpression and knock-down assays were performed to investigate the effects of SANT1 on cis-regulation of SLC47A2. We verified the direct binding between SANT1 and SFPQ/E2F1/HDAC1 using the cross-linking and immunoprecipitation (CLIP) assay. Chromatin immunoprecipitation was performed to confirm the molecular mechanism via which SANT1 activates the transcription of the SLC47A2 coding region. We observed that SANT1 can cis-regulate its own genetic locus. In tumour-adjacent tissues, the SLC47A2 locus highly expresses SANT1, which can remove the regulatory SFPQ/E2F1/HDAC1 suppressor complex from the promoter region, thereby significantly increasing the levels of the H3K27ac modification and RNAPII binding. Owing to a low SANT1 level, the binding of this inhibitory complex in the promoter region is upregulated in RCC, which results in silencing of the SLC47A2 coding region. In conclusion, we identified a novel lncRNA and elucidated the mechanism via which it regulates SLC47A2 expression in RCC.