Linc01776在椎间盘退行性变中生物学功能的研究

目的:椎间盘退行性变(intervertebral disc degeneration, IVDD)是中老年人中的高发病率与高致残率的疾病,目前其病理生理机制尚未完全研究清楚。本实验旨在研究linc01776在IVDD中的差异性表达,并通过生物信息学探索调控IVDD的分子学机制,从而为IVDD的治疗提供作用靶点。方法:根据Pffirrmann评分,将退变椎间盘标本分成对照组与IVDD组,通过qRT-PCR验证linc01776在退变椎间盘中的差异表达;构建Linc01776敲除质粒表达载体,并研究Linc01776在IVDD中生物功能学研究;预测Linc01776参与的竞争性内源RNA (CeRNA)调控机制。结果:linc01776在退变椎间盘中表达显著增加。敲除linc01776后,Aggrecan表达增加,MMP3、MMP13表达减少,细胞外基质分解降低。通过生物信息学预测Linc01776/miR-196b-5p/Akt1的CeRNA机制调控通路。结论:Linc01776促进髓核细胞外基质降解,调控IVDD的发生与发展。Linc01776/miR-196b-5p/Akt1信号轴可能为其调控IVDD进程的CeRNA机制调控通路。     

长链非编码RNA Linc00673过表达对胃癌MGC-803细胞增殖与凋亡的影响*

目的: 探讨长链非编码RNA Linc00673过表达对胃癌细胞增殖和凋亡的影响及其机制。方法: 将重组慢病毒表达质粒pLVX-Linc00673和对照空载体质粒pLVX-NC在293T细胞中进行慢病毒包装与扩增,将重组慢病毒转染胃癌细胞MGC-803建立稳定过表达 Linc00673的细胞系,实时荧光定量PCR方法检测Linc00673基因的表达; MTT实验和克隆形成实验观察细胞的生长增殖;流式细胞术检测细胞周期和细胞凋亡;qPCR检测细胞周期相关调控基因表达;免疫印迹法检测PI3K/Akt信号通路关键分子及肿瘤增殖相关蛋白的表达。结果: Linc00673在胃癌细胞系MGC-803、BGC-823和AGS中的表达量显著高于正常胃粘膜细胞GES-1(P＜0.05)。建立了稳定过表达Linc00673的MGC-803细胞系,Linc00673的表达量比对照空载体组高200倍。Linc00673过表达促进MGC-803细胞增殖和克隆形成(P＜0.05),抑制细胞凋亡并影响细胞周期G1→S期进程(P＜0.01);Linc00673过表达可影响MGC-803细胞周期调节基因CCNG2、p19和CDK1的表达;免疫印迹结果显示,Linc00673过表达不仅促进PI3K/Akt信号通路关键分子pAKT及其下游靶点NF-κB和Bcl-2蛋白的表达,而且上调肿瘤相关因子β-catenin和EZH2蛋白的表达。结论: Linc00673过表达可能通过PI3K/Akt信号通路促进MGC-803细胞增殖、抑制凋亡。     

Clinicopathological and prognostic significance of LINC00673 in human malignancy: a review and meta-analysis

Background: We conducted this research to investigate the relationship between long intergenic non-protein coding RNA 673 (linc00673) expression and prognosis and clinicopathological parameters in human malignancies.Methods: The PubMed, Embase, WOS, and CNKI databases were used to collect eligible research data before 4 January 2021. Meta-analysis was performed using Stata 12.0 software. Pooled odds ratios (ORs) or hazard ratios (HRs) and their 95% confidence interval (CIs) were calculated to evaluate the association of linc00673 expression with survival outcomes and clinical parameters.Results: We finally included 17 articles and a total of 1539 cases for the meta-analysis. The results indicated that linc00673 was significantly correlated with T stage (P=0.006), tumor stage (P<0.001), lymph node metastasis (P<0.001), and distant metastasis (P<0.001). In addition, the results suggested that elevated linc00673 expression predicted a poor overall survival (OS) time (P=0.013) and acted as an independent prognostic factor (P<0.001) for OS in patients with malignancy. Although potential evidence of publication bias was found in the studies on OS in relation to tumor stage in the multivariate analysis, the trim-and-fill analysis confirmed that the results remained stable.Conclusions: Overexpression of linc00673 was significantly correlated with shorter OS time in patients with malignant tumors. Moreover, the increased expression level of linc00673 was significantly correlated with T stage, tumor stage, lymph node metastasis, and distant metastasis. The results presented in this article revealed that linc00673 might be involved in the progression and invasion of malignancy and serve as a novel prognostic biomarker and potential therapeutic target for malignancy.     

IGF2BP2 enhances LincRNA01116 stability via m6A: A potential biomarker and therapeutic target for patients with pre-eclampsia

Pre-eclampsia (PE) is a serious complication in pregnant women characterized by failure of placental remodeling and is one of the primary causes of changes in the placental structure and function. The aberrant expression of long noncoding RNA is associated with the occurrence and progression of PE. This study found that linc01116 expression was significantly downregulated in PE patients and was related to poor uterine spiral artery remodeling. Knockdown of linc01116 remarkably decreased the angiogenesis of trophoblast cells in vitro and in vivo. Mechanistically, IGF2BP2 regulated linc01116 RNA stability via m⁶A methylation. Bioinformatics and other experiments further revealed that linc01116 upregulates AAMP expression by adsorbing miR-210-3p in trophoblast cells. In conclusion, this study revealed the critical role of linc01116 in regulating trophoblast angiogenesis. Furthermore, the study provides new clues for detecting placental pathology in PE.     

Long noncoding RNA Linc00339 promotes triple-negative breast cancer progression through miR-377-3p/HOXC6 signaling pathway

Recently, long noncoding RNAs (lncRNAs) have become the key gene regulators and prognostic biomarkers in various cancers. Through microarray data, Linc00339 was identified as a candidate oncogenic lncRNA. We compared the expression levels of Linc00339 in several breast cancer cell lines and normal mammary gland epithelial cell line. The effects of Linc00339 on tumor progression were examined both in vitro and in vivo. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were applied to evaluate the functions of Linc00339, miR-377-3p, and HOXC6 on cell proliferation. Flow cytometry analysis was used to detect apoptosis and cell cycle distribution. Overall survival (OS) was analyzed using data from The Cancer Genome Atlas and molecular taxonomy of breast cancer international consortium (METABRIC). Dual luciferase assay and RNA immunoprecipitation were performed to confirm the interaction between Linc003339 and miR-377-3p. Linc00339 was increased in breast cancer cell lines compared with the normal epithelial cell. Through in vitro and in vivo experiments, Linc00339 overexpression promoted triple-negative breast cancer (TNBC) proliferation, inhibited cell cycle arrest, and suppressed apoptosis. Silencing of Linc00339 obtained the opposite effects. Mechanistic investigations demonstrated that Linc00339 could sponge miR-377-3p and regulate its expression. Higher expression of miR-377-3p indicated longer OS in breast cancer patients, especially in TNBC patients. Overexpression of miR-377-3p retarded TNBC cell growth through regulating cell cycle distribution and apoptosis. And miR-377-3p was involved in Linc00339-mediated TNBC proliferation through regulating HOXC6 expression. Knockdown of HOXC6 inhibited TNBC progression. In conclusion, our results illuminated that the novel Linc00339/miR-377-3p/HOXC6 axis played a critical role in TNBC progression and might be a promising therapeutic target for TNBC treatment.