Long Non-Coding RNAs as Competitive Endogenous RNAs in Osteosarcoma

Molecular Biology - It was more than twenty years ago that miRNAs were recognized as a new class of RNA, but the understanding of their regulatory role is just beginning to emerge. Furthermore, it...     

长链非编码RNAs与妇科肿瘤

长链非编码RNAs(long non-codiong RNAs,lncRNAs)是具有原始或是剪切转录本功能的RNA,并不符合小分子RNAs和结构RNAs的已知定义。它们分别在宫颈癌、卵巢癌、子宫内膜癌、乳腺癌等妇科肿瘤中出现异常表达的现象,使其有希望成为未来妇科肿瘤的新型标志物和治疗靶点,但其作用机制有待于进一步探索。     

基于RNA-Seq的长非编码RNA预测

随着新一代生物技术和生物信息学的发展,研究发现,在真核生物转录组中存在大量长非编码RNA(long non-codingRNA,lncRNA),而这些lncRNA可能在基因表达调控过程中起到关键性的功能作用.当前lncRNA研究主要采用高通量RNA-Seq测序技术,并通过生物信息学方法对测序数据进行处理和分析,以挖掘其中lncRNA的序列、结构、表达及功能等信息.本文将对基于RNA-Seq的lncRNA预测流程进行介绍,对其中涉及的生物信息学方法进行较为全面的综述,就相关问题和挑战展开讨论,并对研究进行展望.     

Integrative Analysis of Normal Long Intergenic Non-Coding RNAs in Prostate Cancer

Recently, large numbers of normal human tissues have been profiled for non-coding RNAs and more than fourteen thousand long intergenic non-coding RNAs (lincRNAs) are found expressed in normal human tissues. The functional roles of these normal lincRNAs (nlincRNAs) in the regulation of protein coding genes in normal and disease biology are yet to be established. Here, we have profiled two RNA-seq datasets including cancer and matched non-neoplastic tissues from 12 individuals from diverse demography for both coding genes and nlincRNAs. We find 130 nlincRNAs significantly regulated in cancer, with 127 regulated in the same direction in the two datasets. Interestingly, according to Illumina Body Map, significant numbers of these nlincRNAs display baseline null expression in normal prostate tissues but are specific to other tissues such as thyroid, kidney, liver and testis. A number of the regulated nlincRNAs share loci with coding genes, which are either co-regulated or oppositely regulated in all cancer samples studied here. For example, in all cancer samples i) the nlincRNA, TCONS_00029157, and a neighboring tumor suppressor factor, SIK1, are both down regulated; ii) several thyroid-specific nlincRNAs in the neighborhood of the thyroid-specific gene TPO, are both up-regulated; and iii) the TCONS_00010581, an isoform of HEIH, is down-regulated while the neighboring EZH2 gene is up-regulated in cancer. Several nlincRNAs from a prostate cancer associated chromosomal locus, 8q24, are up-regulated in cancer along with other known prostate cancer associated genes including PCAT-1, PVT1, and PCAT-92. We observe that there is significant bias towards up-regulation of nlincRNAs with as high as 118 out of 127 up-regulated in cancer, even though regulation of coding genes is skewed towards down-regulation. Considering that all reported cancer associated lincRNAs (clincRNAs) are biased towards up-regulation, we conclude that this bias may be functionally relevant.     

Gene-Centromere Mapping in Rainbow Trout: High Interference over Long Map Distances

Ten enzyme loci were mapped in relation to their centromeres in gynogenetic diploid rainbow trout. Gene-centromere map distances, calculated under the assumption of complete interference, range from 1.1 cM for Ldh4 to 50 cM for Sod1. The Idh2 and Est1 loci are linked on the same chromosome arm.—The observation of close to 100% heterozygous gynogenetic diploids for the Sod1 and Mdh3,4 loci suggests that near-complete interference occurs on the chromosome arms carrying these loci. The high interference observed in this study and in several other species of fish may be related to the small size of fish chromosome arms.—Comparisons of map locations for the Ldh3 and Ldh4 and the Mdh3 and Mdh4 loci, which were duplicated by a tetraploid event in the evolution of salmonid fish, reveal that they are located at similar distances from their centromeres. Comparative mapping of loci duplicated longer ago shows more variation in map location.—The high proportion of heterozygotes for some loci after gynogenesis involving second polar body retention demonstrates that this is not a practical method for producing homozygous inbred lines in rainbow trout; treatments suppressing the first cell division are more promising for this purpose.     

Long Intergenic Non-Coding RNAs (LincRNAs) Identified by RNA-Seq in Breast Cancer

In an attempt to find the correlation of aberrant expression of long intergenic noncoding RNAs (lincRNAs) with cancer, twenty-five samples of breast cancer tissue and respective adjacent normal tissue were studied for the expression of lincRNAs by RNA-seq. Among the 538 lincRNAs studied, 124 lincRNAs were exclusively expressed in cancer adjacent tissues and 62 lincRNAs were exclusively expressed in the cancer tissues. Furthermore, the expression of 134 lincRNAs was higher while 272 lower in breast cancer tissue compared with adjacent tissue. The expression of four selected lincRNAs (BC2, BC4, BC5, and BC8) was validated by semi-quantitative and real-time PCR. It was revealed that expression of lincRNA-BC5 was positively correlated with patients'' age, pathological stage, and progesterone receptor concentration, while lincRNA-BC8 was negatively correlated with progesterone receptor expression. Higher expression of lincRNA-BC4 was seen in advanced breast cancer grade. LincRNA-BC2 showed no specific changes in the pathological features studied. Interactions between selected lincRNAs and breast cancer associated proteins were highly suggested by RPIseq based on the specific secondary structure. The results demonstrated that this group of lincRNAs was aberrantly expressed in breast cancer. They might play important roles in the function of oncogenes or tumor suppressors affecting the development and progression of breast cancer.     

Rise of the RNA Machines: Exploring the Structure of Long Non-Coding RNAs

Novel, profound and unexpected roles of long non-coding RNAs (lncRNAs) are emerging in critical aspects of gene regulation. Thousands of lncRNAs have been recently discovered in a wide range of mammalian systems, related to development, epigenetics, cancer, brain function and hereditary disease. The structural biology of these lncRNAs presents a brave new RNA world, which may contain a diverse zoo of new architectures and mechanisms. While structural studies of lncRNAs are in their infancy, we describe existing structural data for lncRNAs, as well as crystallographic studies of other RNA machines and their implications for lncRNAs. We also discuss the importance of dynamics in RNA machine mechanism. Determining commonalities between lncRNA systems will help elucidate the evolution and mechanistic role of lncRNAs in disease, creating a structural framework necessary to pursue lncRNA-based therapeutics.     

The Use of Three Long Non-Coding RNAs as Potential Prognostic Indicators of Astrocytoma

Long noncoding RNAs (lncRNAs) are pervasively transcribed and play a key role in tumorigenesis. The aim of the study was to determine the lncRNA expression profile in astrocytomas and to assess its potential clinical value. We performed a three-step analysis to establish the lncRNA profile for astrocytoma: a) the lncRNA expression was examined on 3 astrocytomas as well as 3 NATs (normal adjacent tissues) using the lncRNA microarray; b) the top-hits were validated in 40 astrocytomas (WHO grade II-IV) by quantitative real time-PCR (qRT-PCR); c) the hits with significant differences were re-evaluated using qRT-PCR in 90 astrocytomas. Finally, 7 lncRNAs were found to have a significantly different expression profile in astrocytoma samples compared to the NAT samples. Unsupervised clustering analysis further revealed the potential of the 7-lncRNA profile to differentiate between tumors and NAT samples. The upregulation of ENST00000545440 and NR_002809 was associated with advanced clinical stages of astrocytoma. Using Kaplan-Meier survival analysis, we showed that the low expression of BC002811 or XLOC_010967, or the high expression of NR_002809 was significantly associated with poor patient survival. Moreover, Cox proportional hazard regression analysis revealed that this prognostic impact was independent of other clinicopathological factors. Our results indicate that the lncRNA profile may be a potential prognostic biomarker for the prediction of post-surgical outcomes.