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Objective:To investigate the effect of lncRNA SNHG6 on the proliferation and radiotherapy sensitivity of cervical cancer SiHa cells and its potential mechanism.Methods:The expression levels of lncRNA SNHG6 and miR-485-3p in cervical cancer tissues, paracancer tissues, SiHa cells and SiHa cells exposed to X-ray were detected. The relationship between lncRNA SNHG6 and miR-485-3p was analyzed. After overexpression or knockdown of SNHG6 and miR-485-3p, cell proliferation ability, number of invasion and apoptosis rate were determined by MTT, Transwell chamber assay and flow cytometry, respectively. The effect of miR-485-3p on the Wnt/β-catenin pathway and the effect of XAV939 on SiHa cell proliferation and radiation sensitivity were analyzed.Results:lncRNA SNHG6 was highly expressed in cervical cancer tissues and SiHa cells, whereas was lowly expressed in X-ray irradiated SiHa cells. miR-485-3p was lowly expressed in cervical cancer tissues and SiHa cells, whereas was highly expressed in X-ray irradiated SiHa cells. lncRNA SNHG6 targeted miR-485-3p. Down-regulation of lncRNA SNHG6 expression inhibited cell proliferation and invasion, and enhanced its sensitivity to X-ray radiotherapy, while miR-485-3p inhibitor transfected cells exerted the opposite effect. The up-regulation of lncRNA SNHG6 promoted the proliferation and invasion of SiHa cells through miR-485-3p, and reduced the sensitivity of radiotherapy. Down-regulation of miR-485-3p activated the Wnt/β-catenin pathway, promoted cell proliferation and invasion of SiHa, and reduced its radiation sensitivity to X-ray.Conclusion:Overexpression of lncRNA SNHG6 targeting miR-485-3p activates the Wnt/β-catenin pathway to regulate the proliferation and radiotherapy sensitivity of SiHa cells.
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OBJECTIVE@#To investigate the role of long-chain non-coding RNA MALAT1 in modulating paclitaxel resistance in breast cancer cells.@*METHODS@#Breast cancer SK-BR-3 cells were treated with gradient concentrations of paclitaxel to induce paclitaxel resistance of the cells. The resistant cells were transfected with si-NC, si-MALAT1, pcDNA, pcDNA-MALAT1, miRNC, miR-485-3p mimics, si-MALAT1+anti-miR-NC, or si-MALAT1+anti-miR-485-3p liposomes. Following the transfections, the cells were examined for changes in IC of paclitaxel using MTT assay; the protein expression of P-gp, Bcl-2 and Bax were detected with Western blotting, and a dual luciferase reporter assay was used to detect the binding of MALAT1 to miR-485-3p.@*RESULTS@#Compared with paclitaxel-sensitive SK-BR-3 cells, paclitaxel-resistant SK-BR-3 cells showed significantly increased the IC of paclitaxel with up-regulated MALAT1 expression and down-regulated miR-485-3p expression ( < 0.05). Silencing MALAT1 or overexpressing miR-485-3p obviously lowered the IC of paclitaxel and the expression of P-gp and Bcl-2 and increased the expression of Bax in SK-BR-3/PR cells ( < 0.05). miR-485-3p was identified as the target of MALAT1, and inhibiting miR-485-3p significantly reverse the effect of MALAT1 silencing on IC of paclitaxel and the expressions of P-gp, Bcl-2 and Bax in SK-BR-3/PR cells ( < 0.05).@*CONCLUSIONS@#MALAT1 can modulate paclitaxel resistance in breast cancer cells possibly by targeting miR-485-3p to down-regulate P-gp and Bcl-2 and up-regulate Bax.
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Humans , Cell Line, Tumor , MicroRNAs , Paclitaxel , RNA, Long Noncoding , GeneticsABSTRACT
Objective To investigate whether miR?485?3p plays a role in regulation of radiosensitivity of gastric cancer cells by targeting TLR1. Methods Quantitative real?time PCR and Western blot were used to determine the expression of miR?485?3p and TLR1, respectively. The interaction between miR?485?3p and TLR1 was verified by target prediction software ( DIANA, TargetScan, and miRanda) and dual luciferase reporter assay. Gastric cancer MGC803 cells transfected with miR?485?3p mimic or TLR1 siRNA were exposed to irradiation. Apoptosis assay, colony formation assay, and MTT assay were used to evaluate the changes in radiosensitivity of gastric cancer cells. Dual luciferase reporter assay was used to determine the effects of miR?485?3p overexpression and TLR1 silencing on the activity of NF?κB. Western blot was used to study the effects of miR?485?3p overexpression and TLR1 silencing on NF?κB target genes. Results In gastric cancer cells exposed to radiation, the expression of miR?485?3p was downregulated and the expression of TLR1 was upregulated. TLR1 was predicted to be the target of miR?485?3p by target prediction software. Dual luciferase reporter assay further confirmed TLR1 as the direct target of miR?485?3p. miR?485?3p negatively regulated the expression of TLR1. The overexpression of miR?485?3p, as well as TLR1 silencing, increased the apoptosis rate of cells, reduced colony formation and cell proliferation, and enhanced the radiosensitivity of the cells. Both miR?485?3p overexpression and TLR1 silencing reduced the activity of NF?κB and downregulated the expression of multiple NF?κB target genes. Conclusions miR?485?3p enhances the radiosensitivity of gastric cancer cells probably by targeting TLR1 and regulating the NF?κB signaling pathway.