Recently, more than 1000 large intergenic noncoding RNAs (lincRNAs) have been reported. These RNAs are evolutionarily conserved in mammalian genomes and thus presumably function in diverse biological processes. Here, we report the identification of lincRNAs that are regulated by p53. One of these lincRNAs (lincRNA-p21) serves as a repressor in p53-dependent transcriptional responses. Inhibition of lincRNA-p21 affects the expression of hundreds of gene targets enriched for genes normally repressed by p53. The observed transcriptional repression by lincRNA-p21 is mediated through the physical association with hnRNP-K. This interaction is required for proper genomic localization of hnRNP-K at repressed genes and regulation of p53 mediates apoptosis. We propose a model whereby transcription factors activate lincRNAs that serve as key repressors by physically associating with repressive complexes and modulate their localization to sets of previously active genes.

A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response

Computational Analysis of Microarray Data

Dysfunctions of long non-coding RNA (lncRNAs) have been associated with the initiation and progression of hepatocellular carcinoma (HCC), but the clinicopathologic significance and potential role of lncRNA PTTG3P (pituitary tumor-transforming 3, pseudogene) in HCC remains largely unknown. We compared the expression profiles of lncRNAs in 3 HCC tumor tissues and adjacent non-tumor tissues by microarrays. In situ hybridization (ISH) and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to assess the level of PTTG3P and prognostic values of PTTG3P were assayed in two HCC cohorts (n = 46 and 90). Artificial modulation of PTTG3P (down- and over-expression) was performed to explore the role of PTTG3P in tumor growth and metastasis in vitro and in vivo. Involvement of PTTG1 (pituitary tumor-transforming 1), PI3K/AKT signaling and its downstream signals were validated by qRT-PCR and western blot. We found that PTTG3P was frequently up-regulated in HCC and its level was positively correlated to tumor size, TNM stage and poor survival of patients with HCC. Enforced expression of PTTG3P significantly promoted cell proliferation, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, PTTG3P knockdown had opposite effects. Mechanistically, over-expression of PTTG3P up-regulated PTTG1, activated PI3K/AKT signaling and its downstream signals including cell cycle progression, cell apoptosis and epithelial-mesenchymal transition (EMT)-associated genes. Our findings suggest that PTTG3P, a valuable marker of HCC prognosis, promotes tumor growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in HCC and might represent a potential target for gene-based therapy.

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The long non-coding RNA PTTG3P promotes cell growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in hepatocellular carcinoma.

Thyroid cancer continues to be the most common malignancy of endocrine glands. The incidence of thyroid cancer has risen significantly over the past 4 decades and has emerged as a major health issue. In recent years, significant progress has been achieved in our understanding of the molecular mechanisms of thyroid carcinogenesis, resulting in significant diagnostic, prognostic and therapeutic implications; yet, it has not reached a satisfactory level. Identifying novel molecular therapeutic targets and molecules for diagnosis and prognosis is expected to advance the overall management of this common malignancy. Long noncoding RNAs (lncRNAs) are implicated in the regulation of various key cellular genes involved in cell differentiation, proliferation, cell cycle, apoptosis, migration and invasion mainly through modulation of gene expression. Recent studies have established that lncRNAs are deregulated in thyroid cancer. In this review, we discuss extensively the tumor-suppressive (for example, LINC00271, MEG3, NAMA, PTCSC1/2/3, etc.) and oncogenic (for example, ANRIL, FAL1, H19, PVT1, etc.) roles of various lncRNAs and their possible disease associations implicated in thyroid carcinogenesis. We briefly summarize the strategies and mechanisms of lncRNA-targeting agents. We also describe the potential role of lncRNAs as prospective novel therapeutic targets, and diagnostic and prognostic markers in thyroid cancer.

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Long noncoding RNAs: emerging players in thyroid cancer pathogenesis

Whole-transcriptome analyses have revealed that a large proportion of the human genome is transcribed in non-protein-coding transcripts, designated as long non-coding RNAs (lncRNAs). Rather than being "transcriptional noise", increasing evidence indicates that lncRNAs are key players in the regulation of many biological processes, including transcription, post-translational modification and inhibition and chromatin remodeling. Indeed, lncRNAs are widely dysregulated in human cancers, including hepatocellular carcinoma (HCC). Functional studies are beginning to provide insights into the role of oncogenic and tumor suppressive lncRNAs in the regulation of cell proliferation and motility, as well as oncogenic and metastatic potential in HCC. A better understanding of the molecular mechanisms and the complex network of interactions in which lncRNAs are involved could reveal novel diagnostic and prognostic biomarkers. Crucially, it may provide novel therapeutic opportunities to add to the currently limited number of therapeutic options for HCC patients. In this review, we summarize the current status of the field, with a focus on the best characterized dysregulated lncRNAs in HCC.

The Role of Long Non-Coding RNAs in Hepatocarcinogenesis.

Background: In recent years, long non-coding RNAs (lncRNAs) have been shown to play a critical regulatory role in cancer biology. However, the contribution of lncRNAs to papillary thyroid cancer (PTC) remains largely unknown. Methods: RNA sequencing and quantitative reverse transcription polymerase chain reaction were used to detect and verify changes to the transcriptome profile in 12 PTC tissues compared to paired normal adjacent tissues. The statistical correlation between differentially expressed lncRNAs and clinicopathologic characteristics was analyzed, and potential lncRNA functions were predicted by examining annotations for the co-expressed mRNAs. Furthermore, the specific subgroup patterns of the PTC transcriptome remodeled by BRAF mutations were also analyzed. Results: A total of 188 lncRNAs and 505 mRNAs were differentially expressed in 50% or more of the PTC tissues (fold change >2; p < 0.05) as assessed by RNA-sequencing compared with paired normal adjacent tissues. Forty-seven lncRNAs and 3...

Identification of Specific Long Non-Coding RNA Expression: Profile and Analysis of Association with Clinicopathologic Characteristics and BRAF Mutation in Papillary Thyroid Cancer

Hepatocellular carcinoma (HCC) is one of the most prevalent and aggressive malignancies worldwide. Studies seeking to advance the overall understanding of lncRNA profiling in HCC remain rare. The transcriptomic profiling of 12 HCC tissues and paired adjacent normal tissues was determined using high-throughput RNA sequencing. Fifty differentially expressed mRNAs (DEGs) and lncRNAs (DELs) were validated in 21 paired HCC tissues via quantitative real-time PCR. The correlation between the expression of DELs and various clinicopathological characteristics was analyzed using Student’s t-test or linear regression. Co-expression networks between DEGs and DELs were constructed through Pearson correlation co-efficient and enrichment analysis. Validation of DELs’ functions including proliferation and migration was performed via loss-of-function RNAi assays. In this study, we identified 439 DEGs and 214 DELs, respectively, in HCC. Furthermore, we revealed that multiple DELs, including NONHSAT003823, NONHSAT056213, NONHSAT015386 and especially NONHSAT122051, were remarkably correlated with tumor cell differentiation, portal vein tumor thrombosis, and serum or tissue alpha fetoprotein levels. In addition, the co-expression network analysis between DEGs and DELs showed that DELs were involved with metabolic, cell cycle, chemical carcinogenesis, and complement and coagulation cascade-related pathways. The silencing of the endogenous level of NONHSAT122051 or NONHSAT003826 could significantly attenuate the mobility of both SK-HEP-1 and SMMC-7721 HCC cells. These findings not only add knowledge to the understanding of genome-wide transcriptional evaluation of HCC but also provide promising targets for the future diagnosis and treatment of HCC.

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Profiling, clinicopathological correlation and functional validation of specific long non-coding RNAs for hepatocellular carcinoma.

The invention discloses a kit for detecting drug resistance genes of ten trimethoprim drugs. The kit comprises an amplification primer combination for carrying out specific amplification on the drug resistance genes of the ten trimethoprim drugs and a specific probe for detecting on the drug resistance genes of the ten trimethoprim drugs. The invention further discloses a method for detecting thedrug resistance genes of the ten trimethoprim drugs by using the kit. The method for detecting the drug resistance genes of the trimethoprim drugs and the kit thereof have the characteristics of highintegration degree, high sensitivity, good specificity, stable and reliable detection results and low cost, can be widely used for distribution and epidemiological monitoring of the drug resistance genes of the trimethoprim drugs, and provides an effective tool for rational drug use and effective reduction and delay of drug resistance.

Method and kit for detecting drug resistance genes of ten trimethoprim drugs

The invention discloses a kit for detecting drug resistance genes of 20 dfrA methoxy benzylamine pyrimidine drugs. The kit comprises a amplification primer combination for specifically amplifying drugresistance genes of 20 dfrA methoxy benzylamine pyrimidine drugs and also comprises specific probes for detecting drug resistance genes of 20 dfrA methoxy benzylamine pyrimidine drugs. The inventionalso provides a method of detecting drug resistance genes of 20 dfrA methoxy benzylamine pyrimidine drugs by employing the kit. Various drug resistance genes are detected at the same time in a PCR amplification reaction at one time, and a step of being hybrized with the specific probes, so that the specificity of detection is improved greatly. The method and kit are convenient and rapid, and the detection cost is also lowered greatly.

Method of detecting drug resistance genes of 20 dfrA methoxy benzylamine pyrimidine drugs and kit used

The invention discloses a specific primer and probe combination for detecting four types of drug-resistant genes of glycopeptide drugs in gram positive bacteria. The combination comprises a primer combination for performing specific amplification on the four types of drug-resistant genes of the glycopeptide drugs, and also comprises a specific probe for detecting the four types of drug-resistant genes of the glycopeptide drugs. Meanwhile, the invention discloses a method for detecting the four types of drug-resistant genes of the glycopeptide drugs by using the specific primer and probe combination. The specific primer and probe combination has the advantages of high specificity and coverage degree, can be used for the high-specificity, high-sensitivity, fast and synchronous detection on the drug-resistant genes of vanF, vanI, vanJ and vanO of environment samples of soil, water bodies and the like, particularly in farm places of livestock, poultry, aquatic products and the like; the distribution and transfer conditions of relevant drug-resistant genes are monitored; the specific primer and probe combination can also be used for detecting the drug-resistant genes of vanF, vanI, vanJand vanO in animal or human body infection samples.

Meng Xiaohua

Papers

Identification of Specific Long Non-Coding RNA Expression: Profile and Analysis of Association with Clinicopathologic Characteristics and BRAF Mutation in Papillary Thyroid Cancer

Profiling, clinicopathological correlation and functional validation of specific long non-coding RNAs for hepatocellular carcinoma.

Method and kit for detecting drug resistance genes of ten trimethoprim drugs

Method of detecting drug resistance genes of 20 dfrA methoxy benzylamine pyrimidine drugs and kit used

Specific primer and probe combination for detecting four types of drug-resistant genes of glycopeptide drugs in gram positive bacteria and application