SNHG10/miR-141-3p/WTAP axis promotes osteosarcoma proliferation and migration.

LncRNAs have been suggested to participate in the growth and metastasis of cancer through a variety of molecular mechanisms. Recently, SNHG10, a newly discovered lncRNA, is reported to play a role of an oncogene in osteosarcoma (OS) genesis. Nonetheless, the mechanism underlying OS remains unclear. The present work found that SNHG10 expression increased within OS cells and tissues, while suppressing its expression decreased OS cell proliferation, migration, invasion, but increased their apoptosis. As for the mechanism, we confirmed that SNHG10 could bind to miR-141-3p, while the latter could bind to WTAP. SNHG10 upregulated WTAP through decreasing miR-141-3p expression. More importantly, SNHG10 deletion remarkably reduced proliferation, migration, and invasion of cells, but accelerated their apoptosis. However, when cells were subjected to miR-141-3p inhibitor cotransfection or overexpressed WTAP, these effects were partially recovered. In summary, this study suggested that the expression of SNHG10 markedly elevated within OS, and the SNHG10/miR-141-3p/WTAP axis facilitated OS progression.

Long noncoding RNA CRNDE functions as a diagnostic and prognostic biomarker in osteosarcoma, as well as promotes its progression via inhibition of miR-335-3p.

BACKGROUND: This study was performed to evaluate the diagnostic and prognostic value, as well as the role of long-chain noncoding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) in osteosarcoma (OS). MATERIALS AND METHODS: A quantitative real-time polymerase chain reaction assay was to determine lncRNA CRNDE and microRNA-335-3p (miR-335-3p) expressions. The Kaplan-Meier analysis was to analyze the relationship between lncRNA CRNDE expression and survival in patients with OS. Receiver operating characteristic curves were to evaluate the diagnostic value of lncRNA CRNDE in OS. Bioinformatics analysis and luciferase reporter assays were used to predict and confirm the relationship between lncRNA CRNDE and miR-335-3p. Cell counting Kit-8 and transwell migration assays assessed the role of lncRNA CRNDE and miR-335-3p in OS cells. RESULTS: lncRNA CRNDE expression was upregulated and miR-355-3p expression was downregulated in OS. In patients with OS, low lncRNA CRNDE expression demonstrated higher overall survival, whereas high lncRNA CRNDE expression was an independent poor prognostic factor. Furthermore, increased lncRNA CRNDE expression was associated with distant metastasis and the tumor-node-metastasis stage in patients with OS, which can be considered as an independent diagnostic biomarker in OS. We revealed that miR-335-3p was the target of lncRNA CRNDE. It also demonstrated that knockdown of lncRNA CRNDE inhibited OS cell proliferation, migration, and invasion, and inhibition of miR-355-3p promoted this effect. Finally, miR-335-3p partially mediated the stimulatory effects of lncRNA CRNDE in OS. CONCLUSION: We demonstrated that lncRNA CRNDE is a potential diagnostic and prognostic biomarker for OS, and the lncRNA CRNDE/miR-335-3p axis participates in OS progression.

circ­LRP6 contributes to osteosarcoma progression by regulating the miR­141­3p/HDAC4/HMGB1 axis.

Circular RNA­lipoprotein receptor 6 (circ­LRP6) serves a role in promoting the tumorigenesis of retinoblastoma, esophageal squamous cell cancer and oral squamous cell carcinoma; however, whether circ­LRP6 demonstrates the same effect in osteosarcoma (OS) is yet to be fully elucidated. The present study aimed to analyze the expression, role and potential molecular mechanism of circ­LRP6 in OS. The expression levels of circ­LRP6, microRNA (miR)­141­3p, histone deacetylase 4 (HDAC4) and high mobility group protein 1 (HMGB1) were evaluated by reverse transcription-quantitative PCR in OS tissues and cell lines. Cell Counting Kit­8, Transwell and Matrigel assays were conducted to evaluate cell proliferation, migration and invasion, respectively. Western blotting was also performed to determine HDAC4 and HMGB1 protein expression levels. Bioinformatics and dual­luciferase reporter assays were used to predict and analyze the interactions between circ­LRP6 and miR­141­3p, miR­141­3p and HDAC4, as well as between miR­141­3p and HMGB1. Additionally, RNA immunoprecipitation was performed to verify the association between circ­LRP6 and miR­141­3p. The results confirmed that circ­LRP6 was highly expressed in OS tissues and cell lines. In addition, circ­LRP6 negatively regulated the expression of miR­141­3p and, in turn, miR­141­3p negatively regulated HDAC4 and HMGB1 expression. Functional assays revealed that circ­LRP6 knockdown inhibited the proliferation, migration and invasion of OS cells, whereas the inhibition of miR­141­3p or the overexpression of either HDAC4 or HMGB1 partly reversed the inhibitory effect of circ­LRP6 knockdown. In summary, the present study determined that circ­LRP6 knockdown inhibited the proliferation, migration and invasion of OS cells by regulating the miR­141­3p/HDAC4/HMGB1 axis.