长非编码RNA与蛋白质的相互作用

长非编码RNA(long non-coding RNA,lncRNA)是一类长度大于200个核苷酸但缺乏蛋白质编码潜力的调控型RNA。lncRNA在真核生物基因组中广泛转录,并且能够在多种层次以灵活的方式对基因表达进行调控。lncRNA能够与染色质修饰复合物及转录因子等蛋白质相互作用,这种相互作用提高了基因表达调控的灵活性和复杂性。本文将介绍部分具有代表性的lncRNA-蛋白质相互作用及其在基因表达调控中的作用。     

长链非编码RNA 在乳腺癌中的研究进展

乳腺癌是女性最常见的恶性肿瘤之一,且其发病率呈逐年上升的趋势,尽管随着诊疗技术的进步,乳腺癌的死亡率得到了实质性的降低,但它仍是女性肿瘤死亡的第二大原因,目前对乳腺癌的治疗还面临很大的挑战。长链非编码RNA(Longnon-codingRNA,LncRNA)是一类长度超过200个核苷酸的非编码RNA分子,缺乏开放的阅读框,无编码蛋白质的功能。近年来研究发现,LncRNA可能在多种恶性肿瘤的发生、发展、侵袭及转移过程中起调控作用,且目前对其与乳腺癌的关系研究较多,对LncRNA与乳腺癌相关性的研究有望为乳腺癌的诊治提供新思路。现就LncRNA在乳腺癌中的研究进展做一综述。     

Genome-wide analysis of long non-coding RNAs in Pichia pastoris during stress by RNA sequencing

Long non-coding RNAs play significant roles in many biological processes. The roles of lncRNAs in Pichia pastoris remain unclear. In this work, we focused on the identification of lncRNAs in P. pastoris and exploration of their potential roles in stress response to PLA₂ overexpression and methanol induction. By strand specific RNA sequencing, 208 novel long non-coding RNAs were identified and analyzed. Bioinformatic analysis showed potential trans-target genes and cis-regulated genes of 39 differential lncRNAs. Functional annotation and sequence motif analysis indicated that lncRNAs participate in pathways related to methanol degradation and production of the recombinant protein. The differential expression of lncRNAs was validated by qRT-PCR. Lastly, the potential functions of three lncRNAs were evaluated by knockdown of their expression and analysis of the expression levels of target genes. Our study identifies novel lncRNAs in P. pastoris induced during use as a bioreactor, facilitating future functional research.     

胃癌组织长链非编码RNA ZDHHC8P1、MEG3、TUG1表达与临床病理特征及预后的关系研究

目的:探讨胃癌组织长链非编码RNA(lncRNA)DHHC型锌指蛋白8假基因1(ZDHHC8P1)、母系表达基因3(MEG3)、牛磺酸上调基因1(TUG1)表达与临床病理特征和预后的关系。方法:选取2013年1月至2016年1月我院病理科收集的83例胃癌患者经手术切除或胃镜活检的癌组织及癌旁组织石蜡标本,检测胃癌和癌旁组织中ZDHHC8P1、MEG3、TUG1表达。分析ZDHHC8P1、MEG3、TUG1表达与胃癌临床病理特征的关系。随访所有患者,分析ZDHHC8P1、MEG3、TUG1表达与患者预后的关系。结果:胃癌组织中ZDHHC8P1、TUG1表达量均高于癌旁组织(P0.05),MEG3表达量低于癌旁组织(P0.05)。ZDHHC8P1表达与肿瘤直径、分化程度、浸润深度、TNM分期、淋巴结转移、远处转移有关(P0.05),MEG3、TUG1表达与分化程度、浸润深度、淋巴结转移有关(P0.05)。Kaplan-Meier生存曲线分析结果显示ZDHHC8P1、TUG1高表达患者无疾病进展生存(PFS)率、总生存(OS)率低于ZDHHC8P1、TUG1低表达患者(P0.05),MEG3低表达患者PFS、OS率低于MEG3高表达患者(P0.05)。Cox风险回归分析结果显示淋巴结转移、ZDHHC8P1高表达、TUG1高表达、MEG3低表达是胃癌患者不良预后的危险因素(HR=1.613、1.956、2.512、-0.824,P0.05)。结论:胃癌组织中ZDHHC8P1、TUG1呈高表达,MEG3呈低表达,ZDHHC8P1、TUG1、MEG3表达均与胃癌临床病理特征和预后有关,可作为胃癌患者预后评估的辅助指标。     

Reconstructing the coding and non-coding RNA regulatory networks of miRNAs and mRNAs in breast cancer

microRNAs (miRNAs) are a class of small non-coding RNAs that deregulate and/or decrease the expression of target messenger RNAs (mRNAs), which specifically contribute to complex diseases. In our study, we reanalyzed an integrated data to promote classification performance by rebuilding miRNA–mRNA modules, in which a group of deregulated miRNAs cooperatively regulated a group of significant mRNAs. In five-fold cross validation, the multiple processes flow considered the biological and statistical significant correlations. First, of statistical significant miRNAs, 6 were identified as core miRNAs. Second, in the 13 significant pathways enriched by gene set enrichment analysis (GSEA), 705 deregulated mRNAs were found. Based on the union of predicted sets and correlation sets, 6 modules were built. Finally, after verified by test sets, three indexes, including area under the ROC curve (AUC), Accuracy and Matthews correlation coefficients (MCCs), indicated only 4 modules (miR-106b-CIT-KPNA2-miR-93, miR-106b-POLQ-miR-93, miR-107-BTRC-UBR3-miR-16 and miR-200c-miR-16-EIF2B5-miR-15b) had discriminated ability and their classification performance were prior to that of the single molecules. By applying this flow to different subtypes, Module 1 was the consistent module across subtypes, but some different modules were still specific to each subtype. Taken together, this method gives new insight to building modules related to complex diseases and simultaneously can give a supplement to explain the mechanism of breast cancer (BC).