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Competitive endogenous RNA (ceRNA) is a transcript that can be mutually regulated at the post-transcriptional level by competing shared miRNAs. The ceRNA network connects the function of protein-encoded mRNA with the function of non-coding RNA, such as microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). However, compared with the ceRNA, the identification and combined analysis of lncRNAs, mRNAs, miRNAs, and circRNAs in the cashmere fineness have not been completed. Using RNA-seq technology, we first identified the miRNAs presented in Liaoning Cashmere Goat (LCG) skin, and then analyzed the mRNAs, lncRNAs, circRNAs expressed in LCG and Inner Mongolia cashmere goat (MCG) skin. As a result, 464 known and 45 new miRNAs were identified in LCG skin. In LCG and MCG skin, 1222 differentially expressed mRNAs were identified, 170 differentially expressed lncRNAs and 32 differentially expressed circRNAs were obtained. Then, qRT-PCR was used to confirm further the representative lncRNAs, mRNAs, circRNAs and miRNAs. In addition, miRanda predicted the relationships of ceRNA regulatory network among lncRNAs, circRNAs, miRNAs and mRNAs, the potential regulatory effects were investigated by Go and KEGG analysis. Through the screening and analysis of the results, the ceRNA network regulating cashmere fineness was constructed. LncRNA MSTRG14109.1 and circRNA452 were competed with miRNA-2330 to regulated the expression of TCHH, KRT35 and JUNB, which may provide a potential basis for further research on the process of regulating the cashmere fineness. [ABSTRACT FROM AUTHOR]

Summary: Exploring the regulatory mechanism played by endogenous rice miRNAs in defense responses against the blast disease is of great significance in both resistant variety breeding and disease control management. We identified rice defense‐related miRNAs by comparing rice miRNA expression patterns before and after Magnaporthe oryzae strain Guy11 infection. We discovered that osa‐miR164a expression reduced upon Guy11 infection at both early and late stages, which was perfectly associated with the induced expression of its target gene, OsNAC60. OsNAC60 encodes a transcription factor, over‐expression of which enhanced defense responses, such as increased programmed cell death, greater ion leakage, more reactive oxygen species accumulation and callose deposition, and upregulation of defense‐related genes. By using transgenic rice over‐expressing osa‐miR164a, and a transposon insertion mutant of OsNAC60, we showed that when the miR164a/OsNAC60 regulatory module was dysfunctional, rice developed significant susceptibility to Guy11 infection. The co‐expression of OsNAC60 and osa‐miR164a abolished the OsNAC60 activity, but not its synonymous mutant. We further validated that this regulatory module is conserved in plant resistance to multiple plant diseases, such as the rice sheath blight, tomato late blight, and soybean root and stem rot diseases. Our results demonstrate that the miR164a/OsNAC60 regulatory module manipulates rice defense responses to M. oryzae infection. This discovery is of great potential for resistant variety breeding and disease control to a broad spectrum of pathogens in the future. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is a clinically and molecularly heterogeneous disease, with variation in outcomes only partially predicted by grade and stage. Additional tools to distinguish indolent from aggressive disease are needed. Phenotypic characteristics of stemness correlate with poor cancer prognosis. Given this correlation, we identified single-nucleotide polymorphisms (SNPs) of stemness-related genes and examined their associations with PCa survival. SNPs within stemness-related genes were analyzed for association with overall survival of PCa in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Significant SNPs predicted to be functional were selected for linkage disequilibrium analysis and combined and stratified analyses. Identified SNPs were evaluated for association with gene expression. SNPs of CD44 (rs9666607), ABCC1 (rs35605 and rs212091) and GDF15 (rs1058587) were associated with PCa survival and predicted to be functional. A role for rs9666607 of CD44 and rs35605 of ABCC1 in RNA splicing regulation, rs212091 of ABCC1 in miRNA binding site activity and rs1058587 of GDF15 in causing an amino acid change was predicted. These SNPs represent potential novel prognostic markers for overall survival of PCa and support a contribution of the stemness pathway to PCa patient outcome. [ABSTRACT FROM AUTHOR]

A new regulatory class of small endogenous RNAs called circular RNAs (circRNAs) has been described as miRNA sponges in animals. Using 16 Arabidopsis thaliana RNA-Seq data sets, we identified 803 circRNAs in RNase R-/non-RNase R-treated samples. The results revealed the following features: Canonical and noncanonical splicing can generate circRNAs; chloroplasts are a hotspot for circRNA generation; furthermore, limited complementary sequences exist not only in introns, but also in the sequences flanking splice sites. The latter finding suggests that multiple combinations between complementary sequences may facilitate the formation of the circular structure. Our results contribute to a better understanding of this novel class of plant circRNAs. [ABSTRACT FROM AUTHOR]

Our previous study indicated that lapatinib induces p27-dependent G1 arrest through both transcriptional and post-translational mechanisms. Using miRNA microarray technology and quantitative RT-PCR, we further investigated the potential miRNAs that involved in p27 upregulation and Her-2 signaling pathway alteration with lapatinib treatment. A subset of 7 miRNAs was significantly affected in both 0.5 µM and 2.0 µM and 24 h and 48 h lapatinib treatment. Among them, only miR-1470, miR-126, and miR-1208 were identified in the Her-2 pathway after KEGG pathway analysis. However, luciferase reporter assay confirmed that miR-1470 directly recognized the 3′-untranslated region of c-jun transcripts, which was consistent with TargetScan analysis. miR-1470 significantly decreased c-jun expression, thus miR-1470 may repressc-jun activation of cyclinD1 expression, and consequently promoted the upregulation of p27, a key molecule in the cell cycle arrest. Taken together, the present study provided the first evidences that miR-1470 mediated lapatinib induced p27 upregulation by targeting c-jun. J. Cell. Physiol. 230: 1630-1639, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company [ABSTRACT FROM AUTHOR]

Lin28B is a RNA-binding protein that inhibits the let-7 microRNA family and acts as an oncogene in various human malignant diseases. Conversely, the members of let-7 family function as tumor suppressers and are often inactivated in cancers. The interaction of Lin28B/let-7 plays a crucial part of tumorigenesis. In this study, the authors examined the Lin28B expression using immunohistochemistry in 190 breast cancers and analyzed the correlation of Lin28B immunostaining and clinicopathological characteristics. Breast cancer patients previously diagnosed with invasive ductal carcinomas were enrolled in this study. All cases went through surgical procedures as the initial treatment. The characteristics of every case were collected, including tumor size, pathologic grade, metastatic lymphoid nodes, and estrogen receptor α (ERα), progesterone receptor (PR), and HER2 status. The immunostaining was scored by two independent investigators. Eighty-three (43.7%) of 190 cases showed positive expression of Lin28B. Lin28B immunostaining was increased in tumors compared with the adjacent tissues. Overexpression of Lin28B was linked to poor differentiation, advanced-stage disease, and Ki67-positive status (all p<0.05). Besides, Lin28B expression was significantly different among breast cancer subtypes. This study addresses the role of Lin28B in breast cancers and provides insight of its predictive effects in disease development. [ABSTRACT FROM AUTHOR]

Genetic variants in human microRNA (miRNA) genes may alter mature miRNA processing and/or target selection, and likely contribute to cancer susceptibility and disease progression. Previous studies have suggested that miR-101 may play important roles in the development of cancer by regulating key tumor-associated genes. However, the role of single nucleotide polymorphisms (SNPs) of miR-101 in breast cancer susceptibility remains unclear. In this study, we genotyped 11 SNPs of the miR-101 genes (including miR-101-1 and miR-101-2) in a case-control study of 1064 breast cancer cases and 1073 cancer-free controls. The results revealed that rs462480 and rs1053872 in the flank regions of pre-miR-101-2 were significantly associated with increased risk of breast cancer (rs462480 AC/CC vs AA: adjusted OR = 1.182, 95% CI: 1.030–1.357, P = 0.017; rs1053872 CG/GG vs CC: adjusted OR = 1.179, 95% CI: 1.040–1.337, P = 0.010). However, the remaining 9 SNPs were not significantly associated with risk of breast cancer. Additionally, combined analysis of the two high-risk SNPs revealed that subjects carrying the variant genotypes of rs462480 and rs1053872 had increased risk of breast cancer in a dose-response manner (Ptrend = 0.002). Compared with individuals with “0–1” risk allele, those carrying “2–4” risk alleles had 1.29-fold risk of breast cancer. In conclusion, these findings suggested that the SNPs rs462480 and rs1053872 residing in miR-101-2 gene may have a solid impact on genetic susceptibility to breast cancer, which may improve our understanding of the potential contribution of miRNA SNPs to cancer pathogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Published data on the association between the rs895819 (A>G) polymorphism in the terminal loop of pre-miR-27a and cancer risk is inconclusive. Therefore, we conducted a meta-analysis to estimate the association between this polymorphism and cancer. The PubMed, Web of science, and Embase databases were searched for articles on the hsa-miR-27a rs895819 polymorphism and cancer risk published up to November 24, 2012. The genotype data obtained in the searches were pooled in our meta-analysis, and pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the association. Seven studies with a total of 3849 cases and 4781 controls were eligible for analysis. Overall, we found no significant associations between the hsa-miR-27a rs895819 (A>G) polymorphism and cancer susceptibility (homozygote model: OR=0.88, 95% CI: 0.68–1.14; heterozygote model: OR=0.96, 95% CI: 0.79–1.17; dominant model: OR=0.94, 95% CI: 0.79–1.12; recessive model: OR=0.88, 95% CI: 0.69–1.12). In the subgroup analysis by ethnicity, we found that the rs895819 AG genotype was associated with a decreased risk of cancer in white individuals (dominant model: OR=0.85, 95% CI: 0.76–0.94; heterozygote model: OR=0.84, 95% CI: 0.75–0.94). This meta-analysis indicated that the hsa-miR-27a rs895819 polymorphism did not correlate with overall cancer risk in the general population. However, the rs895819 AG genotype may protect against the development of cancer in white individuals. Larger, better studies of homogeneous cancer patients are needed to further assess the correlation between this polymorphism and cancer risk. [Copyright &y& Elsevier]

AbstractObjective:To identify the signatures of miRNAs differentially expressed in HER2(+) versus HER2(−) breast cancers that accurately predict the HER2 status of breast cancer, and to provide further insight into breast cancer therapy.Methods:By the methods of literature search, aberrant expressed miRNAs were collected. By target prediction algorithm of TargetScan and PicTar and the data enrichment analysis, target gene sets of miRNAs differentially expressed in HER2(+) versus HER2(−) breast cancers were built. Then, using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database, the function modules of Gene Ontology categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) and BIOCARTA pathway, biological functions and signaling pathways that are probably regulated by miRNAs, were analyzed.Results:We got five sets of miRNAs expressed in different HER2 status of breast cancers finally. The five sets of data contain 22; 32; 3; 38; and 62 miRNAs, respectively. After miRNAs target prediction and data enrichment, 5,734; 22,409; 1,142; 22,293; and 43,460 target genes of five miRNA sets were collected. Gene ontology analysis found these genes may be involved in transcription, protein transport, angiogenesis, and apoptosis. Moreover, certain KEGG and BIOCARTA signaling pathways related toHER2 status were found.Conclusion:Using TargetScan and PicTar for data enrichment, and DAVID database, Gene Ontology categories, KEGG and BIOCARTA pathway for analysis of miRNAs different expression, we conducted a new method for biological interpretation of miRNA profiling data in HER2(+) versus HER2(−) breast cancers. It may improve understanding the regulatory roles of miRNAs in different molecular subtypes of breast cancers. Therefore, it is beneficial to improve the accuracy of experimental efforts to breast cancer and potential therapeutic targets. [ABSTRACT FROM AUTHOR]