LncRNA LINC00987通过靶向miR-375抑制肺癌细胞的增殖、侵袭和迁移

目的 探讨IncRNA LINC00987对肺癌细胞增殖、侵袭和迁移的影响.方法 以正常肺泡上皮细胞HPAEPIC为对照,qRT-PCR检测肺癌细胞株A549、HCC827和H1299中LINC00987表达量,选择表达差异较大的A549细胞进行后续实验.将A549细胞分为pcDNA-control组、pcDNA-LI...     

LINC00511过表达促进宫颈癌HeLa细胞的增殖、迁移和侵袭

目的:研究长链非编码RNA(LncRNA)LINC00511过表达对宫颈癌HeLa细胞增殖、迁移和侵袭能力的影响并探索其潜在机制。方法:利用荧光定量PCR（qRT-PCR）及Western blotting检测宫颈癌HeLa细胞中LINC00511 mRNA和蛋白表达;利用细胞转染试验过表达宫颈癌细胞中的LINC00511,利用CCK-8检测法、Transwell实验探究过表达LINC00511对宫颈癌HeLa细胞增殖、迁移和侵袭的影响;通过Western blotting检测HeLa细胞中EMT相关蛋白的表达情况,探究潜在作用机制。结果:HeLa细胞中LINC00511 mRNA和蛋白表达水平显著高于正常宫颈内皮细胞（P＜0.001）;CCK-8法及Transwell实验显示,过表达LINC00511促进了宫颈癌HeLa细胞的增殖、迁移和侵袭能力（P＜0.01）;Western blotting检测显示,过表达LINC00511后宫颈癌HeLa细胞中E-cadherin蛋白表达水平显著下调,而Vimentin 和 α-SMA蛋白表达水平显著上调（P＜0.05）。结论:宫颈癌HeLa细胞中LINC00511显著高表达,可能是宫颈癌潜在的癌基因,LINC00511过表达可促进宫颈癌HeLa细胞的增殖、迁移和侵袭,可能通过调控 EMT过程来调控宫颈癌细胞的生物学行为。     

抑制lncRNA LINC01503通过靶向调控miR-335-5p对肺癌细胞活力、迁移和侵袭的影响及其机制研究

目的:探讨长链非编码RNA(lncRNA)LINC01503对肺癌细胞活力、迁移和侵袭的影响及其作用机制。方法:将人肺癌H1299细胞分为si-NC组(转染si-NC)、si-LINC01503组(转染si-LINC01503)、pcDNA组(转染pcDNA)、pcDNA-LINC01503组(转染pcDNA-LINC01503)、miR-NC组(转染miR-NC)、miR-335-5p组(转染miR-335-5p mimics)、si-LINC01503+anti-miR-NC组(共转染si-LINC01503和anti-miR-NC)、si-LINC01503+anti-miR-335-5p组(共转染si-LINC01503和anti-miR-335-5p)、miR-NC+WT-LINC01503组(共转染miR-NC和WT-LINC01503)、miR-NC+MUT-LINC01503组(共转染miR-NC和MUT-LINC01503)、miR-335-5p+WT-LINC01503组(共转染miR-335-5p和WT-LINC01503)和miR-335-5p+MUT-LINC...     

Long Noncoding RNA LINC02163 Accelerates Malignant Tumor Behaviors in Breast Cancer by Regulating the MicroRNA-511-3p/HMGA2 Axis

Long intergenic nonprotein-coding RNA 02163 (LINC02163) has been reported to be upregulated and work as an oncogene in gastric cancer. The aims of the present study were to determine the expression profile and clinical value of LINC02163 in breast cancer. Additionally, the detailed functions of LINC02163 in breast cancer were explored, and relevant molecular events were elucidated. In this study, LINC02163 was upregulated in breast cancer, and its expression level was closely associated with tumor size, lymph node metastasis, and TNM stage. Patients with breast cancer presenting high LINC02163 expression exhibited shorter overall survival than those presenting low LINC02163 expression. Knockdown of LINC02163 resulted in a decrease in breast cancer cell proliferation, migration, and invasion and an increase in cell apoptosis in vitro. In addition, silencing of LINC02163 impeded breast cancer tumor growth in vivo. Mechanistic investigation revealed that LINC02163 served as a competing endogenous RNA for microRNA-511-3p (miR-511-3p) and consequently upregulated the expression of the high-mobility group A2 (HMGA2), a downstream target of miR-511-3p. Intriguingly, miR-511-3p inhibition and HMGA2 restoration counteracted the effects of LINC02163 deficiency on the malignant properties of breast cancer cells. LINC02163 exerts cancer-promoting effects during the initiation and progression of breast cancer via regulation of the miR-511-3p/HMGA2 axis. Our findings add to our understanding of the roles of the LINC02163/miR-511-3p/HMGA2 pathway as a regulator of breast cancer pathogenesis and may be useful in the development of lncRNA-directed cancer diagnosis, prognosis, and therapy.     

The Effect of LINC01296 Expression in Patients with Cancer: A Systematic Review and Meta-Analysis

Background: Recently has been suggested that LINC01296 has an important role in tumor-promoting in different malignancies. We performed first meta-analysis to assess the association between the LINC01296 expression and clinicopathological criteria and the survival of patients with cancers. Methods: Relevant articles Identified by PubMed, EMBASE, Web of Science, and Scopus searching between December 2000 and 28 December 2018. Binomial data were evaluated by the odds ratio (OR) as the rapid statistic. The association between overall survival (OS) and the LINC01296 expression was evaluated using pooling the hazard ratio (HR) with its corresponding 95% confidence interval (CI). Results: Finally, 9 studies with 720 patients with cancer were included. The expression of LINC01296 showed a significant positive association with TNM stage (OR = 2.67, 95% CI = 1.83-3.88), tumor stage (OR= 2.22, 95% CI= 1.34-3.66) and lymph node metastasis (OR = 3.07, 95% CI = 2.23-4.21). A shorter OS was significantly associated with the expression of LINC01296 (HR = 3.95, 95% CI = 2.65-5.25) and lymph node metastasis (HR = 2.39, 95% CI =1.16-3.63). The OS did not show significant association with gender (HR = 0.83, 95% CI = -0.63-2.30) and tumor stage (HR= 2.66, 95% CI= -0.22-5.54). Conclusion: In conclusion, the results of this meta-analysis suggest that the expression of LINC01296 might be considered as a potential biomarker in patients with cancer.     

lncRNA LINC01206调控银屑病角质形成细胞的功能研究

 目的探讨长链非编码RNA(lncRNA)在银屑病细胞周期信号通路中发挥的功能及其作用机制。方法 通过GEO数据库收集银屑病转录组测序数据集进行分析,筛选差异表达的基因;通过细胞信号通路富集分析（KEGG）识别调控银屑病的关键信号通路;利用加权基因共表达网络分析（WGCNA）构建lncRNA与蛋白编码基因共表达网络;通过siRNA在人永生化表皮细胞（HaCaT细胞）中敲低LINC01206,流式细胞术检测细胞周期进程。结果差异表达基因富集分析研究发现细胞周期信号通路的失调参与银屑病发病。lncRNA与蛋白编码基因共表达网络分析表明,LINC01206、LINC01269、LINC01215和LINC02159等通过与细胞周期信号通路关键基因CCNA2、CCNB1和CCNE1的相互作用调控银屑病进程。细胞实验结果显示,siRNA在HaCaT细胞中敲低LINC01206,引起细胞周期G2/M的阻滞。结论lncRNA的表达变化引起银屑病细胞周期失调,细胞周期信号通路中的关键lncRNA有望成为银屑病治疗的靶标     

Contribution of SUN1 Mutations to the Pathomechanism in Muscular Dystrophies

Mutations in several genes encoding nuclear envelope (NE) associated proteins cause Emery–Dreifuss muscular dystrophy (EDMD). We analyzed fibroblasts from a patient who had a mutation in the EMD gene (p.L84Pfs*6) leading to loss of Emerin and a heterozygous mutation in SUN1 (p.A203V). The second patient harbored a heterozygous mutation in LAP2alpha (p.P426L) and a further mutation in SUN1 (p.A614V). p.A203V is located in the N‐terminal domain of SUN1 facing the nucleoplasm and situated in the vicinity of the Nesprin‐2 and Emerin binding site. p.A614V precedes the SUN domain, which interacts with the KASH domain of Nesprins in the periplasmic space and forms the center of the LINC complex. At the cellular level, we observed alterations in the amounts for several components of the NE in patient fibroblasts and further phenotypic characteristics generally attributed to laminopathies such as increased sensitivity to heat stress. The defects were more severe than observed in EDMD cells with mutations in a single gene. In particular, in patient fibroblasts carrying the p.A203V mutation in SUN1, the alterations were aggravated. Moreover, SUN1 of both patient fibroblasts exhibited reduced interaction with Lamin A/C and when expressed ectopically in wild‐type fibroblasts, the SUN1 mutant proteins exhibited reduced interactions with Emerin as well.     

LncRNA LINC00210 regulated radiosensitivity of osteosarcoma cells via miR-342-3p/GFRA1 axis

BackgroundRadiotherapy is an effective strategy for preventing cancer metastasis, including osteosarcoma. However, cancer radioresistance limits the efficiency of radiotherapy. Therefore, it is essential to investigate the mechanism of osteosarcoma radioresistance.MethodsThe osteosarcoma tissues and adjacent healthy tissues were collected from 53 osteosarcoma patients. The expression of LINC00210, miR‐342‐3p, and GFRA1 mRNA were determined using qRT‐PCR. Cell viability, cell apoptosis, and cell surviving fraction were determined by MTT assay, flow cytometry, and colony formation assay, respectively. Western blot was performed to detect the protein levels. Luciferase assay was conducted to verify the relationship between LINC00210, miR‐342‐3p, and GFRA1.ResultsLINC00210 and GFRA1 were up‐regulated, and miR‐342‐3p was down‐regulated in osteosarcoma tissues and cells. The expression of LINC00210 in osteosarcoma was negatively related to miR‐342‐3p expression and positively associated with GFRA1. Besides, there was a negative correlation between LINC00210 and GFRA1 expression in osteosarcoma. Also, LINC00210 and GFRA1 were up‐regulated, and miR‐342‐3p was down‐regulated in osteosarcoma cells exposed to 4 Gy irradiation treatment. Furthermore, either LINC00210 knockdown or miR‐342‐3p overexpression enhanced the radiosensitivity of osteosarcoma cells. Moreover, LINC00210 increased GFRA1 expression via sponging miR‐342‐3p. Additionally, LINC00210 knockdown improved the radiosensitivity of osteosarcoma cells by regulating GFRA1 expression via sponging miR‐342‐3p.ConclusionLINC00210 modulated the radiosensitivity of osteosarcoma cells via the miR‐342‐3p/GFRA1 axis, making LINC00210 a novel target for improving radiotherapy efficiency in osteosarcoma.