Background: Increasing evidence shows that Long non-coding RNAs (lncRNAs) involve in the development and progression processes of various cancers, including papillary thyroid cancer (PTC). In this study, we focused on the regulation function of lncRNA LINC00460 in the development of PTC. Methods: Expression of LINC00460 was detected using quantitative real-time PCR (qRT-PCR) and Western blot assay. Cell proliferation, cell apoptosis and cell invasion were determined through CCK-8 assay, flow cytometry, and Transwell assay, respectively. In addition, target sites were detected by the dual-luciferase reporter gene assay. Results: LINC00460 expression was markedly up-regulated in PTC tissues and cells compared to their corresponding controls by quantitative real-time PCR (qRT-PCR). Meanwhile, LINC00460 knockdown notably inhibited the proliferation capacity, accelerated the apoptosis and down-regulated the invasion-related proteins (MMP-2, MMP-9, ZEB1) expression. In addition, bioinformatics tools predicted that miR-539 both targeted with the 3ʹ-UTR of LINC00460 and MMP-9, which was confirmed by luciferase reporter assay and Western blot. Conclusion: These findings indicated that LINC00460 can modulate MMP-9 expression to promote cell proliferation, invasion and apoptosis through targeting miR-539, suggesting act as an oncogenic RNA in PTC and provide a new therapeutic perspective.

It has been reported that aquaporin 3 (AQP3) expression is associated with the progression of numerous types of cancer and microRNA (miRNA/miR) processing. However, the effects and precise mechanisms of AQP3 in osteosarcoma (OS) have not been fully elucidated. The present study aimed to investigate the interaction between AQP3 and miR-488 in OS. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay was performed to detect the levels of AQP3 and miR-488 in OS tissues and cell lines, respectively. Cell proliferation, invasion and epithelial-mesenchymal transition (EMT) were detected to analyze the biological functions of miR-488 and AQP3 in OS cells. Furthermore, mRNA and protein levels of AQP3 was measured by RT-qPCR and western blot analysis. Furthermore, AQP3 was validated as an miR-488 target using luciferase assays in OS cells. The present study revealed that the miR-488 level was significantly downregulated in OS tissues and cell lines, and that the expression of AQP3 was markedly increased. Notable, the low miR-488 expression level was associated with upregulated AQP3 expression in OS tissues. Furthermore, introduction of miR-488 markedly suppressed the proliferation, invasion and EMT of OS cells. However, miR-488-knockdown increased the proliferation, invasion and EMT of OS cells. The present study demonstrated that miR-488 could directly target AQP3 using bioinformatics analysis and luciferase reporter assays. In addition, AQP3-silencing had similar effects to miR-488 overexpression on OS cells. Overexpression of AQP3 in OS cells partially reversed the inhibitory effects of miR-488 mimic. miR-488 inhibited the proliferation, invasion and EMT of OS cells by directly downregulating AQP3 expression, and miR-488 targeting AQP3 was responsible for inhibition of the proliferation, invasion and EMT of OS cells.

Objective: In this study, we performed an updated meta-analysis by summarizing all available relevant association studies to evaluate whether the murine double minute-2 (MDM2) T309G polymorphism is associated with risk of leukemia and to determine its prognostic effect. Material and Methods: Studies published in PubMed, Embase and the Cochrane Controlled Trial Register were searched till June 2014 using the search terms ‘MDM2', ‘polymorphism' and ‘leukemia'. Results: Eleven studies were included in this meta-analysis, with a total of 2,478 patients accrued. There were 8 studies providing data on single nucleotide polymorphism at position 309 (SNP309) and risk of leukemia and 7 studies providing data on SNP309 and overall survival. Our analysis showed that patients having G/G mutations had a significantly higher risk of developing leukemia (HR 1.90, 95% CI 1.56-2.31, p < 0.00001), while the association between G/T and leukemia was not significant (HR 1.18, 95% CI 0.96-1.45, p = 0.11). In addition, SNP309 was not significantly associated with patient survival (HR 1.29, 95% CI 0.79-2.13, p = 0.31). Conclusions: Our meta-analysis showed that the MDM2 T309G variation, especially homozygous G/G, might be associated with an increased risk of leukemia. Additional studies are needed to confirm the findings as well as to understand the underlying mechanisms.

Background Chemoresistance limits the therapeutic effect of cisplatin (DDP) on non-small cell lung cancer (NSCLC). Circular RNAs (circRNAs) function as important regulators in chemoresistance. This study aimed to explore the regulation of circRNA Phosphatidylinositol-4-Phosphate 5-Kinase Type 1 Alpha (circ_PIP5K1A) in DDP resistance. Methods The expression analysis of circ_PIP5K1A, micoRNA-493-5p (miR-493-5p) and Rho Associated Coiled-Coil Containing Protein Kinase 1 (ROCK1) was conducted through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell sensitivity was determined using 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cell proliferation and cell viability were evaluated by colony formation assay and MTT assay, respectively. Cell cycle and apoptosis detection was performed via flow cytometry. Cell motility was examined by transwell migration or invasion assay. Dual-luciferase reporter assay was applied to confirm the target binding. ROCK1 protein level was assayed via Western blot. In vivo assay was carried out using xenograft model in mice. Results Circ_PIP5K1A level was abnormally increased in DDP-resistant NSCLC tissues and cells. Silencing circ_PIP5K1A reduced DDP resistance, proliferation, cell cycle progression and cell motility in DDP-resistant NSCLC cells. Circ_PIP5K1A directly interacted with miR-493-5p in NSCLC cells. The function of circ_PIP5K1A was dependent on the negative regulation of miR-493-5p. MiR-493-5p directly targeted ROCK1 and circ_PIP5K1A regulated the ROCK1 level via acting as a sponge of miR-493-5p. Overexpression of miR-493-5p inhibited chemoresistance and cancer progression by downregulating ROCK1 expression in DDP-resistant NSCLC cells. Circ_PIP5K1A regulated DDP sensitivity in vivo via the miR-493-5p/ROCK1 axis. Conclusion These findings suggested that circ_PIP5K1A upregulated the ROCK1 expression to promote DDP resistance and cancer progression in NSCLC by sponging miR-493-5p.

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