恶性肿瘤发生发展中小核仁RNA宿主基因15的作用及机制

长链非编码RNA在多种人类肿瘤中扮演重要角色。小核仁RNA宿主基因15(small nuclear RNA host gene 15, SNHG15)作为一个新发现的长链非编码RNA,在胃癌、肝癌、胰腺癌等多种人类肿瘤中高表达。异常表达的SNHG15与患者的临床特征密切相关,并通过不同机制调节肿瘤细胞的增殖、抗凋亡、侵袭和转移。SNHG15有可能成为肿瘤诊断和治疗的潜在靶点。本文就SNHG15在肿瘤发生、发展中的作用及潜在分子机制作一综述。     

长链非编码RNA CRNDE在肿瘤中的研究进展

<正>结直肠差异化表达(CRNDE)RNA属于一种长链非编码RNA(LncRNA),在结直肠癌及多种肿瘤组织中表达上调,被认为是一个原癌基因,其表达与肿瘤患者的预后呈负相关,是一个潜在的生物标志物和治疗靶点。本文就LncRNA CRNDE在肿瘤中的临床意义和作用机制做一简要综述。1 LncRNA CRNDE基本信息LncRNA CRNDE最初被发现在大肠癌组织中高表达,它的基因位于人染色体16q12.2,与IRX5基因相     

lncRNA LINC00460和ADAR1表达与乳腺癌预后的关系及其诊断价值

目的 探讨长链非编码RNA(lncRNA)LINC00460和RNA特异性腺苷脱氨酶1(ADAR1)表达水平与乳腺癌预后的关系及其诊断价值.方法 回顾性收集2019年5月至2020年5月同济大学附属第一妇婴保健院收治的86例乳腺癌患者的乳腺组织和癌旁组织.采用qRT-PCR法测定乳腺癌组织和癌旁组织中LINC00460...     

LINC00978在非小细胞肺癌中的临床价值和生物学作用

目的探究长链非编码RNA(long non-coding RNA, lncRNA)LINC00978在非小细胞肺癌(non-small cell lung cancer, NSCLC)中的表达变化及生物学功能,并初步探讨其作用机制。方法采用qRT-PCR检测NSCLC患者肿瘤组织与血清中LINC00978的表达水平。通过CCK-8、平板克隆、Transwell迁移和侵袭实验观察LINC00978敲减和过表达对A549细胞生物学功能的影响。采用流式细胞术、qRT-PCR和western blot探究LINC00978的作用机制。结果 LINC00978在NSCLC患者肿瘤组织(t=2.465,P0.05)和血清(t=8.781,P0.01)中呈高表达。LINC00978敲减抑制A549细胞增殖、迁移和侵袭能力(P均0.01),诱导G_1期阻滞以及细胞凋亡(P均0.01)。LINC00978敲减下调Cyclin D1和Bcl-2的表达而上调Bax的表达(P均0.05)。此外,LINC00978敲减抑制N-cadherin、Vimentin、Snail、Slug和Twist的表达而促进E-cadherin的表达(P均0.05)。LINC00978过表达则具有相反作用。结论 LINC00978在NSCLC中高表达,并促进NSCLC发生、发展,具有成为NSCLC诊断及治疗新靶点的潜能。     

多发性骨髓瘤非编码RNA的研究进展

非编码RNA(ncRNA)是一类很少或不能合成蛋白质的RNA,包括微小RNA(miRNA)和长链非编码RNA(lncRNA)等RNA。miRNA分子是短的非编码RNA,在实体肿瘤和造血系统恶性肿瘤中有异常表达,在基因表达的转录后调节中起重要的作用。lncRNA在哺乳动物包括人类中,已被证明在癌组织中异常表达并参与致癌或肿瘤抑制的过程。文章就ncRNA在多发性骨髓瘤(MM)中的生物学功能和作为潜在作用靶点的治疗价值作一综述。     

长链非编码RNA与弥漫性大B细胞淋巴瘤关系的研究进展

弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)发病机制未明,治疗效果差,发生率与死亡率仍在不断攀升,因此探究DLBCL的发病机制与发现新的分子诊断标记和治疗靶点尤为重要。长链非编码RNA(long non-coding RNA,lnc RNA)是真核细胞中一类转录本长度大于200 bp的RNA,可在转录水平及转录后水平调控其靶基因的表达,并参与多种肿瘤的发生、发展、侵袭及转移等过程。近年来长链非编码RNA在弥漫性大B细胞淋巴瘤中的作用不断被发现及证实。本文就HULC、PEG10、Linc RNA-p21、HOTAIR、LUNAR1、MALAT1和SubSig Lnc-17等长链非编码RNA与弥漫性大B细胞淋巴瘤的关系做一综述,希望为相关基础研究及临床诊断和治疗提供新思路。     

非编码RNA在恶性血液病中的发病机制及临床意义

现已研究证明,在细胞内能够稳定存在的转录产物中信使RNA不超过2％,其余绝大部分为非编码RNA,而非编码RNA依据其分子的大小又可分为长链非编码RNA和小分子非编码RNA,其经典的作用机制是通过与靶mRNA互补配对,从而促进mRNA的降解或抑制蛋白质的翻译.研究表明,其表达的异常与体内多种肿瘤相关,因此对其功能的深入研究将具有重大的科学意义和临床价值.现就非编码RNA在血液肿瘤中的基础与临床研究进展进行综述.     

长链非编码RNA在血液肿瘤中的研究进展

长链非编码RNA(lncRNA)作为肿瘤发病机制研究领域的热点，其在血液系统恶性肿瘤中的重要性正逐渐被阐明。lncRNA不仅影响细胞增殖、分化、多能性和凋亡等多种生物学过程，调控血液肿瘤发生和进展，而且lncRNA异常表达和突变与耐药和预后密切相关，可作为血液肿瘤的新型生物标志物和潜在治疗靶点。本文将重点介绍lncRNA在血液肿瘤中的最新进展，为血液病的临床诊断、预后评估和靶向药物的研发提供新思路。     

超级增强子长链非编码RNA LINC01232在大肠癌组织中的表达及其对癌细胞生物学行为的影响

目的探讨超级增强子长链非编码RNA(SE-LncRNA)LINC01232在大肠癌组织中的表达水平及其对大肠癌细胞生物学行为的影响。方法通过基因芯片筛选4对大肠癌患者组织(癌组织和癌旁组织)中差异表达的SE-LncRNA,发现LINC01232在癌组织中显著高表达(Fold Change=2.6569,P=0.0258);采用实时荧光定量PCR(RT-qPCR)检测LINC01232在31对大肠癌组织中的表达水平,并分析其与患者临床病理参数的关系;应用ROC曲线分析LINC01232对大肠癌诊断的敏感性和特异性;将2种人大肠癌细胞系HCT-116和HT-29分别设置对照组(NC)和转染LINC01232 Smarter Silence组(si-LINC01232),通过CCK-8试验、细胞克隆形成试验及Transwell试验检测LINC01232对大肠癌细胞增殖、侵袭和迁移等生物学行为的影响;对跨膜蛋白超家族9-2(TM9SF2)与LINC01232在组织中的表达量进行相关性分析,并采用western blot检测下调LINC0123对TM9SF2蛋白表达的影响。结果LINC01232在大肠癌组织中的表达水平显著高于癌旁组织,差异具有统计学意义[(2.015±2.865)vs(1.000±2.036),t=2.388,P=0.023];LINC01232在组织中的表达量与TNM临床分期(χ²=5.427,P=0.020)和远处转移(χ²=4.663,P=0.031)有关;ROC曲线分析结果显示,LINC01232对大肠癌诊断的敏感性为53.13%,特异性为78.13%;与NC组相比,si-LINC01232组细胞的增殖、克隆形成率、侵袭及迁移能力显著降低(P<0.05);在大肠癌组织中,TM9SF2与LINC01232的表达呈正相关(r=0.51,P<0.01),而在大肠癌细胞中,TM9SF2 mRNA和蛋白质水平在LINC01232下调后降低(P<0.05)。结论LINC01232在大肠癌组织中异常高表达,并促进大肠癌细胞的增殖、侵袭和迁移,有望成为大肠癌治疗的新靶点。     

Long noncoding RNA LINC01296 plays an oncogenic role in colorectal cancer by suppressing p15 expression

ObjectiveTo examine the role of the long noncoding RNA LINC01296 in colorectal carcinoma (CRC) and to explore the underlying mechanism.MethodsWe detected LINC01296 expression levels in a cohort of 51 paired CRC and normal tissues. We also assessed the effects of LINC01296 on cell proliferation and apoptosis in CRC cells in vitro, and measured its effect on tumor growth in an in vivo mouse model. We identified the potential downstream targets of LINC01296 and assessed its regulatory effects.ResultsExpression levels of LINC01296 were elevated in 37/51 CRC tissues compared with the corresponding normal tissues and were significantly associated with tumor stage, lymph node metastasis, and distant metastasis. Knockdown of LINC01296 using antisense oligonucleotides inhibited cell proliferation and promoted apoptosis of colon cancer cells in vitro and inhibited tumor growth in vivo. Knockdown of LINC01296 also significantly increased the gene expression of p15 in colon cancer cells. LINC01296-specific suppression of p15 was validated by the interaction between enhancer of zeste homolog 2 and LINC01296.ConclusionOverexpression of LINC01296 suppressed the expression of p15 leading to CRC carcinogenesis. These findings may provide the basis for novel future CRC-targeted therapies.     

LINC00261和miR-522-3p在结直肠癌中的表达及其与患者预后的关系

目的检测长链非编码RNA LINC00261、微小RNA-522-3p(miR-522-3p)在结直肠癌组织中的表达水平,并探讨两者的相关性及其与患者预后的关系。方法收集2013年1月至2014年12月在该院行手术切除治疗的68例结直肠癌组织及其配对的癌旁组织,应用实时荧光定量PCR检测结直肠癌和癌旁组织中LINC00261、miR-522-3p的表达水平;分析LINC00261、miR-522-3p的表达与结直肠癌患者临床病理参数的关系;Kaplan-Meier生存模型分析LINC00261、miR-522-3p表达对结直肠癌患者生存率的影响;多因素Cox回归分析影响结直肠癌患者预后的独立危险因素;Pearson相关分析检测LINC00261与miR-522-3p在结直肠癌组织中表达水平的相关性。结果LINC00261在结直肠癌组织中表达水平低于其在癌旁组织中的表达水平(P<0.05),miR-522-3p在结直肠癌组织中表达水平高于其在癌旁组织中的表达水平(P<0.05)。LINC00261在结直肠癌组织中的表达水平与分化程度、临床分期和淋巴结转移情况相关(P<0.05),miR-522-3p在结直肠癌组织中的表达水平与临床分期和淋巴结转移情况相关(P<0.05)。LINC00261低表达组的预后比LINC00261高表达组预后更差(P<0.05),miR-522-3p高表达组的预后比miR-522-3p低表达组的预后更差(P<0.05)。高临床分期、低分化程度、淋巴结转移、LINC00261低表达和miR-522-3p高表达是结直肠癌患者预后不良的独立危险因素(P<0.05)。结直肠癌组织中LINC00261与miR-522-3p的表达呈负相关(P<0.05)。结论结直肠癌组织中LINC00261表达下调、miR-522-3p表达上调,二者表达呈负相关,且均与结直肠癌患者的不良病理参数和预后相关。LINC00261、miR-522-3p可能是结直肠癌潜在的预后标志物和治疗靶标。     

Small peptide LINC00511-133aa encoded by LINC00511 regulates breast cancer cell invasion and stemness through the Wnt/β-catenin pathway

LINC00511 is an long non-coding RNA (lncRNA) of ncRNAs,This study aimed to investigate whether the lncRNA LINC00511 could encode a small peptide, LINC00511-133aa, and whether this peptide could promote breast cancer cell metastasis and stemness by activating the wnt/β-catenin pathway. The LINC00511-133aa coding sequence vector and control vector were transfected into MCF-7 and MDA-MB-231 breast cancer cells, with subsequent assessment of peptide expression using PCR, western blotting, and immunofluorescence assays. Cell proliferation, invasion, and apoptosis were evaluated using CCK8, apoptotic, wound healing, and transwell invasion assays, while the characteristic changes of tumor stem cells were detected through sphere-forming assay and western blot analyses of the stemness markers Oct4, Nanog, and SOX2. Results showed that LINC00511-133aa was indeed encoded by LINC00511 and promoted the invasiveness and stemness of breast cancer cells while limiting apoptosis by modulating the expression levels of wnt/β-catenin pathway-related proteins Bax, c-myc, and CyclinD1, as well as facilitating β-catenin protein entry into the nucleus. This study provides evidence for the potential involvement of lncRNA LINC00511 and its peptide product in breast cancer progression via the regulation of the wnt/β-catenin pathway.     

LINC01232 serves as a novel biomarker and promotes tumour progression by sponging miR-204-5p and upregulating RAB22A in clear cell renal cell carcinoma

BackgroundLong non-coding RNAs (lncRNAs) are involved in the progression of various cancers, including clear cell renal cell carcinoma (ccRCC). This study aimed to investigate the expression and prognostic value of long intergenic non-protein coding RNA (LINC) 01232 in ccRCC and preliminary explore the molecular mechanism underlying the role of LINC01232 in ccRCC progression.MethodsTumour tissues and adjacent normal tissues of 122 patients with ccRCC were collected in this study. The levels of LINC01232, microRNA (miR)-204-5p and RAB22A were measured by quantitative real-time PCR. The proliferation, migration and invasion of ccRCC cells were detected by cell counting kit-8 assay and Transwell assay, respectively. The interaction among LINC01232, miR-204-5p and RAB22A was confirmed by bioinformatics analysis, dual-luciferase reporter assay and Pearson correlation analysis. The association of LINC01232 and miR-204-5p with ccRCC patient survival was verified by the Kaplan–Meier method and log-rank test. The prognostic value of LINC01232 in ccRCC was confirmed by Cox regression analysis.ResultsLINC01232 expression was increased in ccRCC tumour tissues and ccRCC cells and independently predicted the prognosis of ccRCC patients. In addition, LINC01232 silencing inhibited ccRCC cell proliferation, migration and invasion. Moreover, LINC01232 served as a sponge for miR-204-5p, and miR-204-5p reduction reversed the inhibitory effect of LINC01232 silencing on ccRCC cell function. Furthermore, LINC01232 could sponge miR-204-5p, causing the elevation of RAB22A in ccRCC, thereby promoting ccRCC cell function.ConclusionLINC01232 may be an independent prognostic biomarker in ccRCC and plays an oncogenic role in ccRCC progression by sponging miR-204-5p and upregulating RAB22A.     

Non-coding RNAs as biomarkers in liquid biopsies with a special emphasis on extracellular vesicles in urological malignancies

ABSTRACT

Introduction: Non-coding RNAs (ncRNAs) are important regulators of cellular signaling in tumor-related processes. They can not only be detected in tumor tissues, but also in body fluids. ncRNAs are released into circulation as cell-free RNAs in at least two ways: bound to proteins like Ago2 or packed in extracellular vesicles (EV). Therefore, they have a great potential to serve as biomarkers in liquid biopsies. This review gives an overview of the current knowledge concerning ncRNAs and EVs as putative liquid biomarkers in urological tumor diseases.

Areas covered: Literature was searched for ncRNAs including microRNA, long non-coding RNA, small interfering RNA, small nuclear RNA, small nucleolar RNA and PIWI-interacting RNA in blood (serum, plasma) and urine samples from urological tumor (urothelial, kidney, prostate, testicular germ cell, penile cancer) patients.

Expert opinion: The data demonstrate an important potential of circulating non-coding RNAs as biomarkers in liquid biopsies for diagnosis and follow-up of patients with urological tumors. To translate these markers into clinical practice, independent and prospective validation, standardization of isolation and quantification techniques are inevitable. Another task is the development of predictive ncRNA biomarkers to overcome problems associated with tumor heterogeneity and to select patients individually for systemic therapies.     

Long non-coding RNA DLX6-AS1/miR-141-3p axis regulates osteosarcoma proliferation,migration and invasion through regulating Rab10

Long non-coding RNA (lncRNAs) DLX6-AS1 plays significant roles in various types of malignant tumors, including osteosarcoma (OS), the most prevalent primary malignant bone tumor. However, the role and mechanism of DLX6-AS1 have not been fully illuminated in OS. Here, we aimed to find a novel mechanism for DLX6-AS1 in regulating the development of OS through sponging microRNA (miRNA). According to the luciferase reporter assay, RNA immunoprecipitation and RNA pull-down assay, miRNA (miR)-141-3p can physically interact with DLX6-AS1 and Rab10. The expressions of DLX6-AS1 and Rab10 were upregulated and miR-141-3p was downregulated in OS tissues and cells (MG-63 and U2OS), as described by RT-qPCR and western blotting. Moreover, there was a negative correlation between the expression of miR-141-3p and either DLX6-AS1 or Rab10, and a positive correlation between DLX6-AS1 and Rab10. Functionally, cell proliferation, migration and invasion were evaluated by utilizing the MTT assay and transwell assays. As a result, DLX6-AS1 knockdown suppressed OS cell proliferation, migration and invasion in MG-63 and U2OS cells, which was abolished by the downregulation of miR-141-3p. Similarly, the upregulation of Rab10 not only promoted OS cell progression in vitro, but also blocked the inhibitory effect of miR-141-3p overexpression in OS cells. Notably, DLX6-AS1 knockdown could, in turn, reverse the promoting effect of Rab10 on OS cell progression. Xenograft experiments depicted that DLX6-AS1 knockdown restrained the tumor growth of MG-63 cells in vivo. In conclusion, the knockdown of DLX6-AS1 might suppress OS progression via sponging miR-141-3p and downregulating Rab10, suggesting a novel DLX6-AS1/miR-141-3p/Rab10 pathway in OS progression.

Long non-coding RNA (lncRNAs) DLX6-AS1 plays significant roles in various types of malignant tumors, including osteosarcoma (OS), the most prevalent primary malignant bone tumor.     

LINC00115 regulates lung adenocarcinoma progression via sponging miR-154-3p to modulate Sp3 expression

The most commonly diagnosed and most lethal subtype of lung cancer is lung adenocarcinoma (LUAD). Therefore, more detailed understanding of the potential mechanism and identification of potential targets of lung adenocarcinoma is needed. A growing number of reports reveals that long non-coding RNAs (lncRNAs) play crucial roles in cancer progression. In present study, we found that lncRNA LINC00115 was upregulated in LUAD tissues and cells. Functional studies revealed that LINC00115 knockdown inhibits the proliferation, growth, invasion, and migration of LUAD cells. Mechanically, we indicated that miR-154-3p is target microRNA of LINC00115, and the effect of downregulated LINC00115 on LUAD cells was partially reversed by the miR-154-3p antisense oligonucleotide (ASO-miR-154-3p). Further investigation revealed that Specificity protein 3 (Sp3) directly interacted with miR-154-3p, and the Sp3 level was positively correlated with the LINC00115 expression. Rescue experiments further showed that Sp3 overexpression partially restored the effect of downregulated LINC00115 on LUAD cells. Similarly, in vivo experiments confirmed that downregulated LINC00115 inhibited xenograft growth and Sp3 expression. Our results demonstrated that LINC00115 knockdown inhibited LUAD progression via sponging miR-154-3p to modulate Sp3 expression. These data indicate that the LINC00115/miR-154-3p/Sp3 axis can be a potential therapeutic target of LUAD.