MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

MicroRNAs: Target Recognition and Regulatory Functions

Long non-coding RNAs (lncRNAs) are associated to a plethora of cellular functions, most of which require the interaction with one or more RNA-binding proteins (RBPs); similarly, RBPs are often able to bind a large number of different RNAs. The currently available knowledge is already drawing an intricate network of interactions, whose deregulation is frequently associated to pathological states. Several different techniques were developed in the past years to obtain protein–RNA binding data in a high-throughput fashion. In parallel, in silico inference methods were developed for the accurate computational prediction of the interaction of RBP–lncRNA pairs. The field is growing rapidly, and it is foreseeable that in the near future, the protein–lncRNA interaction network will rise, offering essential clues for a better understanding of lncRNA cellular mechanisms and their disease-associated perturbations.

/pdf/revealing-protein-lncrna-interaction-3ssixtak6x.pdf

Revealing protein–lncRNA interaction

Recently, a novel class of transcripts, long non-coding RNAs (lncRNAs), is being identified at a rapid pace These RNAs have critical roles in diverse biological processes, including tumorigenesis Here we report that taurine-upregulated gene 1 (TUG1), a 71-kb lncRNA, recruiting and binding to polycomb repressive complex 2 (PRC2), is generally downregulated in non-small cell lung carcinoma (NSCLC) tissues In a cohort of 192 NSCLC patients, the lower expression of TUG1 was associated with a higher TNM stage and tumor size, as well as poorer overall survival (P<0001) Univariate and multivariate analyses revealed that TUG1 expression serves as an independent predictor for overall survival (P<0001) Further experiments revealed that TUG1 expression was induced by p53, and luciferase and chromatin immunoprecipitation (ChIP) assays confirmed that TUG1 was a direct transcriptional target of p53 TUG1 knockdown significantly promoted the proliferation in vitro and in vivo Moreover, the lncRNA-mediated regulation of the expression of HOX genes in tumorigenesis and development has been recently receiving increased attention Interestingly, inhibition of TUG1 could upregulate homeobox B7 (HOXB7) expression; ChIP assays demonstrated that the promoter of HOXB7 locus was bound by EZH2 (enhancer of zeste homolog 2), a key component of PRC2, and was H3K27 trimethylated This TUG1-mediated growth regulation is in part due to specific modulation of HOXB7, thus participating in AKT and MAPK pathways Together, these results suggest that p53-regulated TUG1 is a growth regulator, which acts in part through control of HOXB7 The p53/TUG1/PRC2/HOXB7 interaction might serve as targets for NSCLC diagnosis and therapy

/pdf/p53-regulated-long-non-coding-rna-tug1-affects-cell-2lqqtnatvw.pdf

P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression

Long noncoding RNAs: Novel insights into hepatocelluar carcinoma

Targeting self-renewal is an important goal in cancer therapy and recent studies have focused on Notch signalling in the maintenance of stemness of glioma stem cells (GSCs). Understanding cancer-specific Notch regulation would improve specificity of targeting this pathway. In this study, we find that Notch1 activation in GSCs specifically induces expression of the lncRNA, TUG1. TUG1 coordinately promotes self-renewal by sponging miR-145 in the cytoplasm and recruiting polycomb to repress differentiation genes by locus-specific methylation of histone H3K27 via YY1-binding activity in the nucleus. Furthermore, intravenous treatment with antisense oligonucleotides targeting TUG1 coupled with a drug delivery system induces GSC differentiation and efficiently represses GSC growth in vivo. Our results highlight the importance of the Notch-lncRNA axis in regulating self-renewal of glioma cells and provide a strong rationale for targeting TUG1 as a specific and potent therapeutic approach to eliminate the GSC population.

Targeting the Notch-regulated non-coding RNA TUG1 for glioma treatment

CONCLUSION: We identified a set of lncRNAs differentially expressed in gastric cancer, providing useful information for discovery of new biomarkers and therapeutic targets in gastric cancer.

Analysis of long non-coding RNA expression profiles in gastric cancer

Helicobacter pylori antibiotic resistance is a serious concern in China, where it severely influences treatment for H. pylori infection. To overcome this, it is essential to apply personalized therapies based on local or individual data on antibiotic-resistant phenotypes or genotypes. We conducted a large-scale multi-center study with a retrospective cross-sectional observational design to investigate the antibiotic-resistant phenotypes and genotypes of H. pylori in China. Strains were isolated from the gastric biopsy samples of H. pylori-infected patients from five different regions in China. The strains were tested for antibiotic-resistant phenotypes and genotypes, and the agreement between the two was assessed. In total, 4242 H. pylori strains were isolated and cultured, with an 84.43% success rate. The primary and secondary antibiotic resistance rates of H. pylori were 37.00% and 76.93% for clarithromycin, 34.21% and 61.58% for levofloxacin, 2.20% and 6.12% for amoxicillin, 1.61% and 3.11% for furazolidone, 1.18% and 3.31% for tetracycline, and 87.87% and 93.48% for metronidazole, respectively. The dual-resistance patterns for metronidazole/clarithromycin, metronidazole/levofloxacin, and clarithromycin/levofloxacin were 43.6%, 38.4%, and 26.1%, respectively. Clarithromycin- and levofloxacin-resistant H. pylori phenotypes and genotypes showed satisfactory agreement. Based on these findings, clarithromycin- and levofloxacin-resistant genotype testing could partially replace traditional antibiotic susceptibility testing in China. Continuous monitoring and personalized treatments based on individual and local H. pylori antibiotic-resistance data remain necessary.

Yu-Shu Zhang

Papers

Analysis of long non-coding RNA expression profiles in gastric cancer

A retrospective study of the antibiotic-resistant phenotypes and genotypes of Helicobacter pylori strains in China