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The long non-coding RNA (lncRNA) RUSC1-AS1 has been reported to be dysregulated in the progression of many cancers. Also, RUSC1-AS1 had been detected to be highly expressed in laryngeal squamous cell carcinoma and breast cancer cells, suggesting that RUSC1-AS1 may be a biomarker for cancers. However, the biological role and regulatory mechanism of RUSC1-AS1 in hepatocellular carcinoma (HCC) remain unknown. In this study, we found that RUSC1-AS1 was upregulated in HCC tissues and cells, and predicted unfavorable prognosis of HCC patients. The function assays including colony formation, EdU, TUNEL assay revealed that RUSC1-AS1 facilitated HCC cell proliferation and inhibited HCC cell apoptosis. Furthermore, mechanism assays including luciferase reporter assay and RIP assay demonstrated that RUSC1-AS1 could directly bind to hsa-miR-7-5p. Besides, hsa-miR-7-5p targeted and negatively regulated NOTCH3 expression. Moreover, RUSC1-AS1 sponged hsa-miR-7-5p to upregulate NOTCH3 and to trigger the NOTCH signaling pathway. The rescue assays depicted that RUSC1-AS1 regulated HCC cell proliferation and apoptosis through modulating NOTCH signaling. In conclusion, lncRNA RUSC1-AS1 promoted the proliferation and reduced the apoptosis of HCC cells through activation of NOTCH signaling via hsa-miR-7-5p/NOTCH3 axis.

ABSTRACT. Dysregulation of microRNA (miR) is often associated with cancer development and progression. Aberrant expression of miR-134 has been found in some types of cancer. However, its expression and function in osteosarcoma remain unclear. The aim of this study was to explore the effects of miR-134 in osteosarcoma tumorigenesis and development. The expression level of miR-134 was quantified by real-time reverse transcription-polymerase chain reaction in human osteosarcoma cell lines and tissues. The effects of miR-134 on MG-63 cell phenotypes and tumorigenicity in vivo were observed using flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, transwell invasion, migration, and scratch migration assays. MiR-134 was significantly downregulated in osteosarcoma cell lines and clinical specimens. Decreased miR-134 expression was significantly associated with large tumor size, positive distant metastasis, and advanced clinical stage. Low miR-134 expression in osteosarcoma was an independent 16772 Y. Bao et al.©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 16771-16781 (2015) predictor of poor survival. Overexpression of miR-134 inhibited MG-63 cell proliferation, invasion, and migration, promoted cell apoptosis in vitro, and suppressed tumorigenicity in vivo. These findings indicate that miR-134 may act as a tumor suppressor in osteosarcoma and could serve as a novel therapeutic agent for miRNA-based therapy.

Background and Objective. Anaplastic thyroid cancer (ATC) gains the definition as an aggressive tumor that has been found in human beings. It has been put in researches that complex gene interaction networks exert an influence on ATC tumor in terms of occurrence and prognosis. Therefore, this study is conducted with the purpose of recognizing possible key genes that have relation with prognosis and pathogenesis of ATC. Methods. For determining pathways and key genes that have relation with development of ATC, differentially expressed genes (DEGs) from GSE33630 as well as GSE65144 expression microarray were screened. Furthermore, we also worked on carrying out the task of constructing a protein-protein interaction (PPI) network and the work of weighing gene coexpression network (WGCNA). DAVID was utilized for the performance of the Gene Ontology (GO) as well as KEGG pathway enrichment analyses for DEGs. We used TCGA THCA data and GSE53072 to further verify the hub gene and hub pathway. Results. We came to the conclusion of the recognition of a total of 1063 genes as DEGs. Analysis regarding functional and pathway enrichment showed that there existed a notable enrichment of upregulated DEGs in the organization of extracellular structure and matrix organization, as well as in organelle fission and nuclear division. The downregulated DEG was markedly gathered in the thyroid hormone metabolic process and generation, as well as in the metabolic process of cellular modified amino acid. We identified 10 hub genes (CXCL8, CDH1, AURKA, CCNA2, FN1, CDK1, ITGAM, CDC20, MMP9, and KIF11) through the PPI network, which might be strongly linked to the carcinogenesis and the development of ATC. In the coexpression network, 6 modules that were relevant to ATC were recognized. The modules were related to the interaction of signaling pathway of p53, Hippo, PI3K/Akt, and ECM-receptor. This hub genes and hub pathway were further successfully validated as a potential biomarker for carcinogenesis and prediction in another database GSE53072. Conclusion. To summarize, this research displayed an illustration of hub genes and pathways that had relation with ATC development, which suggested that DEGs and hub genes, recognized on the basis of bioinformatics analyses, were valuable in the diagnosis for patients with ATC.