Microphase separation of graft-diblock copolymer by dissipative particle dynamics simulation

Microphase-separation behaviour of graft-diblock copolymers was investigated by the dissipative particle dynamics. Besides familiar totally ordered mesostructures, the simulated phase diagram also shows unfamiliar locally ordered mesostructures together with a few melted morphologies. The simulated order–disorder transition critical value is higher than the theoretically predicted value due mainly to the increasing fluctuation coming from finite chain length. The microphase-separation morphologies in graft-diblock copolymers shift away significantly from that of the corresponding linear ones with the same component volume fractions. Generally, it is more difficult to trigger microphase separation for graft-diblock copolymers than for their linear analogues, in good agreement with theoretical and experimental findings. The change of graft fraction has a significant effect on the microphase-separation behaviour of graft-diblock copolymers.     

长链非编码RNA作为潜在药物靶点的研究进展

随着生命科学的不断发展,2012年DNA元件百科全书（ENCODE）项目进一步丰富了人类基因组功能元件的相关信息。该项目 发现人类基因组超过80%的序列会被转录,其中大部分转录本是非编码RNA（ncRNA）。目前,在这些非编码RNA中,小RNA的研究 相对深入,而长链非编码RNA（lncRNA）的研究相对较少。越来越多研究表明,很多lncRNA参与到人类重大疾病的发生、发展过程之 中,并且一些动物实验证实lncRNA可作为药物靶点。因此,从lncRNA角度筛选新的药物靶点也越来越受到研究者的关注。重点总结了 lncRNA的生物学功能及作为潜在药物靶点的研究进展。     

LncRNA AWPPH as a prognostic predictor in human cancers in Chinese population: evidence from meta-analysis

Background: Long non-coding RNA associated with poor prognosis of hepatocellular carcinoma (AWPPH) is dysregulated in a variety of human cancers. However, the prognostic value of AWPPH in various cancers remains unclear.Methods: Comprehensive literature search was performed in PubMed, Web of Science, CNKI and Wangfang databases, and eligible studies were obtained according to the inclusion and exclusion criteria. The pooled hazard ratios (HRs) and odds ratios (ORs) were applied to assess the clinical value of AWPPH expression for overall survival (OS) and clinicopathological features.Results: A total of 19 articles including 1699 cancer patients were included in the study. The pooled results demonstrated that evaluated AWPPH expression was positively related to a poorer overall survival of patients with cancers (HR = 1.79, 95%CI: 1.44–2.14, P<0.001). Subgroup analysis revealed that tumor type and sample size affect the predictive value of AWPPH on OS, whereas cut-off value and HR estimation method have no impact on it. In addition, the pooled data also showed that AWPPH was positively linked to advanced TNM stage (OR = 2.50, 95%CI: 1.94–3.22, P<0.001), bigger tumor size (OR = 2.64, 95%CI: 1.47–4.73, P=0.001), macro-vascular invasion (OR = 2.08, 95%CI: 1.04–4.16, P=0.04) and lymph node metastasis (OR = 2.68, 95%CI: 1.82–3.96, P<0.001). Moreover, the results of the trim and fill analysis confirmed the reliability of our finding.Conclusions: Up-regulation of AWPPH was associated with advanced TNM stage, bigger tumor size, worse lymph node metastasis, macro-vascular invasion and shorter overall survival, suggesting that AWPPH may serve as a biomarker for prognosis and clinicopathological characteristics in human cancers among the Chinese population.     

Integrated analysis of a competing endogenous RNA network reveals key long noncoding RNAs as potential prognostic biomarkers for hepatocellular carcinoma

Growing evidence has revealed that long noncoding RNAs (lncRNAs) have an important impact on tumorigenesis and tumor progression via a mechanism involving competing endogenous RNAs (ceRNAs). However, their use in predicting the survival of a patient with hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to develop a novel lncRNA expression–based risk score system to accurately predict the survival of patients with HCC. In our study, using expression profiles downloaded from The Cancer Genome Atlas database, the differentially expressed messenger RNAs (mRNAs), lncRNAs, and microRNAs (miRNAs) were explored in patients with HCC and normal liver tissues, and then a ceRNA network constructed. A risk score system was established between lncRNA expression of the ceRNA network and overall survival (OS) or recurrence-free survival (RFS); it was further analyzed for associations with the clinical features of patients with HCC. In HCC, 473 differentially expressed lncRNAs, 63 differentially expressed miRNAs, and 1417 differentially expressed mRNAs were detected. The ceRNA network comprised 41 lncRNA nodes, 12 miRNA nodes, 24 mRNA nodes, and 172 edges. The lncRNA expression–based risk score system for OS was constructed based on six lncRNAs (MYLK-AS1, AL359878.1, PART1, TSPEAR-AS1, C10orf91, and LINC00501), while the risk score system for RFS was based on four lncRNAs (WARS2-IT1, AL359878.1, AL357060.1, and PART1). Univariate and multivariate Cox analyses showed the risk score systems for OS or RFS were significant independent factors adjusted for clinical factors. Receiver operating characteristic curve analysis showed the area under the curve for the risk score system was 0.704 for OS, and 0.71 for RFS. Our result revealed a lncRNA expression–based risk score system for OS or RFS can effectively predict the survival of patients with HCC and aid in good clinical decision-making.     

HOXD-AS1 is a predictor of clinical progression and functions as an oncogenic lncRNAs in papillary thyroid cancer

Long noncoding RNA HOXD cluster antisense RNA 1 (HOXD-AS1) has been found to play a crucial role in the tumorigenesis and progression of human cancer. However, the role of HOXD-AS1 in papillary thyroid cancer is still unknown. The purpose of this study was to investigate the clinical value and biological function of HOXD-AS1 in papillary thyroid cancer. The results showed HOXD-AS1 is overexpressed in papillary thyroid cancer tissues and cell lines compared with matching nontumor tissue specimens and normal thyroid cell line, respectively. High expression of HOXD-AS1 was associated with elderly people, advanced clinical stage, large tumor size, present lymph node metastasis, and distant metastasis. There was no significant correlation between HOXD-AS1 expression and disease-free survival or overall survival in this cohort from the TCGA database. The study in vitro suggested reduced HOXD-AS1 expression inhibited papillary thyroid cancer cell proliferation, migration, and invasion, and promoted cell-cycle arrest. In conclusion, HOXD-AS1 is a biomarker for predicting clinical progression in papillary thyroid cancer.     

lncRNA作为竞争性内源RNA在非小细胞肺癌中的作用

长链非编码RNA(long non-coding RNA,lncRNA)参与肿瘤的多种生理、病理进程.研究表明,lncRNA可通过与微小RNA (microRNA, mi RNA)反应元件相互作用,并与其他RNA分子形成竞争性内源RNA (competing endogenous RNA,ceRNA)的调控网络,参与基因的表达调控.lncRNA以ceRNA方式参与非小细胞肺癌(non-small cell lung cancer,NSCLC)的发生发展过程,为揭示NSCLC的分子机理开拓了新的思路,也为NSCLC的治疗提供新的靶点.本文在课题组前期发现NSCLC相关ceRNA基础上,主要讨论lncRNA作为ceRNA在NSCLC中高表达、低表达及治疗相关方面的作用.     

Unusual semi‐extractability as a hallmark of nuclear body‐associated architectural noncoding RNAs

NEAT1_2 long noncoding RNA (lncRNA) is the molecular scaffold of paraspeckle nuclear bodies. Here, we report an improved RNA extraction method: extensive needle shearing or heating of cell lysate in RNA extraction reagent improved NEAT1_2 extraction by 20‐fold (a property we term “semi‐extractability”), whereas using a conventional method NEAT1_2 was trapped in the protein phase. The improved extraction method enabled us to estimate that approximately 50 NEAT1_2 molecules are present in a single paraspeckle. Another architectural lncRNA, IGS16, also exhibited similar semi‐extractability. A comparison of RNA‐seq data from needle‐sheared and control samples revealed the existence of multiple semi‐extractable RNAs, many of which were localized in subnuclear granule‐like structures. The semi‐extractability of NEAT1_2 correlated with its association with paraspeckle proteins and required the prion‐like domain of the RNA‐binding protein FUS. This observation suggests that tenacious RNA–protein and protein–protein interactions, which drive nuclear body formation, are responsible for semi‐extractability. Our findings provide a foundation for the discovery of the architectural RNAs that constitute nuclear bodies.     

Phase separation of chromatin and small RNA pathways in plants

Gene expression can be modulated by epigenetic mechanisms, including chromatin modifications and small regulatory RNAs. These pathways are unevenly distributed within a cell and usually take place in specific intracellular regions. Unfortunately, the fundamental driving force and biological relevance of such spatial differentiation is largely unknown. Liquid–liquid phase separation (LLPS) is a natural propensity of demixing liquid phases and has been recently suggested to mediate the formation of biomolecular condensates that are relevant to diverse cellular processes. LLPS provides a mechanistic explanation for the self-assembly of subcellular structures by which the efficiency and specificity of certain cellular reactions are achieved. In plants, LLPS has been observed for several key factors in the chromatin and small RNA pathways. For example, the formation of facultative and obligate heterochromatin involves the LLPS of multiple relevant factors. In addition, phase separation is observed in a set of proteins acting in microRNA biogenesis and the small interfering RNA pathway. In this Focused Review, we highlight and discuss the recent findings regarding phase separation in the epigenetic mechanisms of plants.     

Long noncoding RNA HOXD-AS1 induces epithelial-mesenchymal transition in breast cancer by acting as a competing endogenous RNA of miR-421

Breast cancer (BCa) is the most common malignant tumor in females. Long noncoding RNAs (lncRNAs) are deregulated in many types of human cancers, including BCa. The purpose of the present study was to examine the expression profile and biological role of HOXD cluster antisense RNA 1 (HOXD-AS1) in BCa. Our results revealed that HOXD-AS1 was upregulated in BCa tissues and cell lines, and high HOXD-AS1 expression was correlated with aggressive clinicopathological characteristics of BCa patients. Further gain-of-function and loss-of-function analysis showed that HOXD-AS1 overexpression promoted, whereas HOXD-AS1 knockdown inhibited BCa cell proliferation, cell cycle progression, migration, and invasion, indicating that HOXD-AS1 may function as a novel oncogene in BCa. Mechanistically, HOXD-AS1 could activate epithelial-mesenchymal transition (EMT) in BCa cells. We further proved that HOXD-AS1 might serve as a competing endogenous RNA of miR-421 in BCa cells, and miR-421 was downregulated and negatively correlated with HOXD-AS1 expression in BCa tissues. Besides, we confirmed that SOX4, a master regulator of EMT, was a direct target gene of miR-421. Further, rescue experiments suggested that miR-421 overexpression partly abrogated the oncogenic role of HOXD-AS1 in BCa cells. Therefore, we shed light on that HOXD-AS1/miR-421/SOX4 axis may be considered as a novel therapeutic target for the treatment of BCa patients.     

Expression analysis of circulating plasma long noncoding RNAs in colorectal cancer: The relevance of lncRNAs ATB and CCAT1 as potential clinical hallmarks

Long noncoding RNAs (lncRNAs) have been demonstrated to regulate a variety of cell processes and involve in the development and progression of colorectal cancer (CRC). Recently, the circulating lncRNAs have emerged as minimally invasive biomarkers for cancer diagnosis and prognosis. We aimed to examine the plasma expression level of long noncoding RNAs lnc-ATB, lnc-CCAT1, and lnc-OCC-1 in CRC patients and evaluate the clinical values. A total of 74 pretreatment CRC and 74 healthy blood biopsies were subjected to differentially evaluate the expression levels of three lncRNAs (OCC-1, CCAT1, and ATB). Briefly, after plasma separation and total RNA extraction, RNAs were reversely transcribed to complementary DNA followed by amplification using a quantitative real-time polymerase chain reaction technique for lncRNA expression analysis. The results showed that the expression levels of lnc-ATB (p < 0.001) and CCAT1 (p = 0.024), but not OCC-1 (p = 0.24), were significantly upregulated in the CRC compared with the healthy group. The calculated AUC of ROC was 0.78 (95% confidence interval [CI]: 0.811–0.94) for lnc-ATB and 0.64 (95% CI: 0.811–0.94) for CCAT1, which were indicative of a high discriminatory power (p < 0.001). The highest accuracy for lncRNA-ATB was obtained at a cutoff point of 2.5, which corresponded to sensitivity and specificity of 82% and 75%, respectively. Our results suggested a significant accuracy of lncRNA-ATB and lncRNA-CCAT1 in distinguishing CRC patients from healthy individuals.     

LncRNA TP73-AS1 predicts poor prognosis and functions as oncogenic lncRNA in osteosarcoma

TP73 antisense RNA 1 (TP73-AS1), a novel long noncoding RNA (lncRNA), has been suggested to be deregulated in various human cancers and serve as a tumor suppressor or promoter, depending on tumor types. The role of TP73-AS1 in osteosarcoma is still unknown. In our results, TP73-AS1 was highly expressed in osteosarcoma tissue samples and cell lines compared with matching adjacent nontumor tissue specimens and a normal human osteoblast cell line, respectively. Moreover, high expression of TP73-AS1 was statistically associated with advanced Enneking stage, large tumor size, present distant metastasis, and poor histological grade, while exhibiting no statistical association with age, sex, and tumor site. The survival analyses showed that patients with osteosarcoma with high expression of TP73-AS1 obviously had lower overall survival than osteosarcoma patients with low expression of TP73-AS1, and high expression of TP73-AS1 was an independent poor prognostic factor for osteosarcoma patients. The experiments in vitro indicated that inhibition of TP73-AS1 expression depressed osteosarcoma cell viability, migration, and invasion, and arrested cell cycle. In conclusion, TP73-AS1 serves as oncogenic lncRNA participated in osteosarcoma progression.