Advances in the role of natural products in human gene expression / 中国天然药物

Natural products (NPs), especially those from traditional herbal medicines, can evidently modulate human gene expression at multiple levels, leading to a wide diversity of bioactivities. Although numerous bio-functions of NPs for human body have been found, there is little understanding about how NPs achieve it, as less attention was drawn to the definite mechnism by which NPs regulate gene expression. Furthermore, based on the rapidly advancing knowledge of mechanisms for gene regulation in recent years, newly-understood mechanisms, such as post-transcriptional regulation, are found to be involved in NP-elicited bio-effects, providing a new perspective on understanding the role of NPs in gene expression. Therefore, in the current review, we summarize the function of NPs in gene expression from the perspectives of transcriptional, post-transcriptional, and post-translational regulation, which will reinforce the understanding of NP-induced effects in gene expression and facilitate the exploration of more NPs with potential therapeutic effects.

Advances in molecular biology research on human parvovirus B19 / 生物工程学报

Human parvovirus B19 (B19 virus) is one of the two parvoviruses that cause human diseases. As an important pathogen to humans, it causes infectious erythema in children, acute aplastic anemia, fetal edema and death. In this review, we focus on the recent advances in the molecular virology of B19V, such as viral genotypes, viral receptor, genomic features and viral replication, viral transcription and post-transcription regulation, viral nonstructural and structural protein features and functions, viral diagnosis and antiviral agents, to provide reference for further study of B19 pathogenesis mechanisms, treatment and diagnostic strategies.

MicroRNA-383-5p inhibits the progression of gastric carcinoma via targeting HDAC9 expression

MicroRNAs (miRNAs), as post-transcriptional regulators, have been reported to be involved in the initiation and progression of various types of cancer, including gastric cancer (GC). The present study aimed to investigate the role of miR-383-5p in gastric carcinogenesis. Cell viability was analyzed using CCK-8 kit. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was used to evaluate cell apoptosis. The expression levels of miR-383-5p and histone deacetylase 9 (HDAC9) mRNA in GC tissues and cell lines were analyzed using RT-qPCR. The protein expression of HDAC9 was detected by western blotting. We found that HDAC9 was up-regulated and miR-383-5p was down-regulated in GC tissues and cell lines. High HDAC9 expression or low miR-383-5p expression was closely related to poor prognosis and metastasis in GC patients. HDAC9 knockout or miR-383-5p mimics led to growth inhibition and increased apoptosis in AGS and SGC-7901 cells. More importantly, we validated that miR-383-5p as a post-transcriptional regulator inhibited HDAC9 expression and was inversely correlated with HDAC9 expression in GC tissues. miR-383-5p had the opposite effects to HDAC9 in gastric carcinogenesis. miR-383-5p played an important role in gastric carcinogenesis, and it is one of the important mechanisms to regulate oncogenic HDAC9 in GC, which might be helpful in the development of novel therapeutic strategies for the treatment of GC.

RNA-binding protein PTB in spermatogenesis: Progress in studies / 中华男科学杂志

RNA binding proteins (RBPs) regulate the function of cells by interacting with nascent transcripts and therefore are receiving increasing attention from researchers for their roles in tissue development and homeostasis. The polypyrimidine tract binding (PTB) protein family of RBPs are important posttranscriptional regulators of gene expression. Further investigations on the post-transcriptional regulation mechanisms and isoforms of PTB proteins in the spermatogenesis show that PTB protein 1 (Ptbp1) is a predominant isoform in mitotic cells (spermatogonia), while Ptbp2 predominates in meiotic spermatocytes and postmeiotic spermatids and binds to the specific 3' untranslated region (3' UTR) of the phosphoglycerate kinase 2 (Pgk-2) mRNA, which helps to stabilize Pgk-2 mRNA in male mouse germ cells. In case of Ptbp2 inactivation in the testis, the differentiation of germ cells arrests in the stage of round spermatids, with proliferation of multinucleated cells in the seminiferous tubule, increased apoptosis of spermatocytes, atrophy of seminiferous tubules, and lack of elongating spermatids, which consequently affects male fertility. This article presents an overview on the structure of the PTB protein and its role in regulating mammalian spermatogenesis.

Effect and mechanism of miR-206/miR-613 on expression of OATP1B1 / 药学学报

This study was designed to explore the effect and mechanism of miR-206/miR-613 on the expression of OATP1B1 gene. Bioinformatic analysis was used to predict the potential miRNAs target sites in 3'-untranslated region (3'-UTR) of OATP1B1 mRNA. The expression level of miR-206/miR-613 and OATP1B1 mRNA and protein was determined with RT-qPCR and Western blot, respectively. Luciferase assay was used to explore the exact mechanism of the effect of miR-206/miR-613 on the expression of OATP1B1 mRNA and protein. The results showed that the seed sequences of miR-206/miR-613 has perfect complementary with 3'-UTR of OATP1B1 mRNA in terms of sequence specificity. The secondary structure between miR-206/miR-613 and 3'-UTR of OATP1B1 mRNA was rather stable. The OATP1B1 protein level was down-regulated by 24.7%, 38.8% by overexpression of miR-206/miR-613. The expression was up-regulated by 25%, 38.2% by inhibition of miR-206/miR-613. However, overexpression or inhibition of miR-206/miR-613 had no effect on the expression of OATP1B1 mRNA. The luciferase activity of pMIR/OATP1B1-WT luciferase reporter gene was decreased by 35% and 30% through overexpression of miR-206/miR-613. The expression was increased by 33.1% and 32.5% through inhibition of miR-206/miR-613. When the binding sites in the 3'-UTR of OATP1B1 mRNA complementary with miR-206/miR-613 was mutated, overexpression or inhibition of miR-206/miR-613 had no effect on the luciferase activity. Collectively, miR-206/miR-613 post-transcriptionally regulates the expression of OATP1B1 protein by directly targeting the 3'-UTR of OATP1B1 mRNA.

Role of small noncoding RNA in the regulation of bacterial virulence / 华西口腔医学杂志

In the long-term interaction between pathogens and host, the pathogens regulate the expression of related viru-lence genes to fit the host environment in response to the changes in the host microenvironment. Gene expression was believed to be controlled mainly at the level of transcription initiation by repressors or activators. Recent studies have revealed that small noncoding RNAs (sRNAs) are key regulators in bacterial pathogenesis. sRNA in bacteria is a noncoding RNA with length ranging from 50 to 500 nucleotides. Pathogens can sense the changes in the host environment and consequently regulate the expression of virulence genes by sRNAs. This condition promotes the ability of pathogens to survive within the host, which is beneficial to the invasion and pathogenicity of pathogens. In contrast to transcriptional factors, sRNA-mediated gene regu-lation makes rapid and sensitive responses to environmental cues. Many sRNAs involved in bacterial virulence and pathogenesis have been identified. These sRNAs are key components of coordinated regulation networks, playing important roles in regulating the expression of virulence genes at post-transcriptional level. This review aims to provide an overview on the molecular mechanisms and roles of sRNAs in the regulation of bacterial virulence.

Advances in research of microRNA and B-cell lymphoma / 肿瘤研究与临床

MicroRNAs (miRNAs) are a class of small single-stranded and non-coding RNAs that negatively regulate gene expression at the post-transcriptional level by degradation of target mRNA or inhibition of protein translation.Recent studies have shown that miRNAs play important roles in human diseases.It is of great importance to explore the role of miRNAs in the pathogenesis,early diagnosis and new therapeutic strategies of a variety of malignant tumors,including B-cell lymphoma.This review described the biosynthesis of miRNAs,the mechanisms of miRNAs target regulation and the involvement of miRNAs in the initiation and progression of human cancers,and summarized the role of miRNAs in B-cell lymphoma.

Construction of pGL3-TNF-α3′UTR luciferase reporter gene and tanshinone compounds screening / 中国药理学通报

Aim To screen the potential inhibitors of post-transcriptional activity of pro-inflammatory media-tor TNF-α from the lipophilic constituents in Chinese Medicine Salvia miltiorrhiza Bunge ( Danshen) , we es-tablished dual luciferase reporter gene system pGL3-TNF-α3′UTR ( 3′untranslated region ) co-transfected with Renilla control gene. Methods Complementary DNA ( cDNA) template was obtained from human um-bilical vein endothelial cells ( HUVECs ) . The full length DNA of TNF-α 3′-UTR was amplified through PCR, and then connected the luciferase reporter vector pGL3-control after enzyme digestion. pGL3-TNF-α 3′UTR constructs were co-transfected with pSVRenilla into the mononuclear macrophages RAW264. 7 cells. The relative activity of reporter genes was measured by dual luciferase reporter ( DLR ) assay system after the stimulus of lipopolysaccharide ( LPS ) in presence or absence of tanshinones compounds. Results The pGL3-TNF-α3′UTR luciferase reporter gene was suc-cessfully constructed. The cloning DNA fragment and sequence were both consistent with the GENBANK da-tabase. LPS significantly induced the relative reporter activityof RAW264 . 7 cells transfected with pGL3-TNF-α 3′UTR. Among four tanshinones compounds, we found only cryptotanshinone could significantly de-crease LPS-induced relative reporter activity. Conclu-sion The pGL3-TNF-α 3′UTR construct combined with DLR assay system was successfully established, which can be used to discover the agents such as cryp-totanshinone that regulate the post-transcription of TNF-α in treatment of inflammatory and malignant dis-eases.

Control of Inflammatory Responses: a New Paradigm for the Treatment of Chronic Neuronal Diseases

The term 'inflammation' was first introduced by Celsus almost 2000 years ago. Biological and medical researchers have shown increasing interest in inflammation over the past few decades, in part due to the emerging burden of chronic and degenerative diseases resulting from the increased longevity that has arisen thanks to modern medicine. Inflammation is believed to play critical roles in the pathogenesis of degenerative brain diseases, including Alzheimer's disease and Parkinson's disease. Accordingly, researchers have sought to combat such diseases by controlling inflammatory responses. In this review, we describe the endogenous inflammatory stimulators and signaling pathways in the brain. In particular, our group has focused on the JAK-STAT pathway, identifying anti-inflammatory targets and testing the effects of various anti-inflammatory drugs. This work has shown that the JAK-STAT pathway and its downstream are negatively regulated by phosphatases (SHP2 and MKP-1), inhibitory proteins (SOCS1 and SOCS3) and a nuclear receptor (LXR). These negative regulators are controlled at various levels (e.g. transcriptional, post-transcriptional and post-translational). Future study of these proteins could facilitate the manipulation of the inflammatory response, which plays ubiquitous, diverse and ambivalent roles under physiological and pathological conditions.

Regulation of luteinizing hormone receptor expression by an RNA binding protein: Role of ERK signaling.

A specific luteinizing hormone receptor (LHR) mRNA binding protein (LRBP) has been identified and purified. This LH receptor mRNA binding protein selectively binds to the polypyrimidine rich bipartite sequence in the coding region of the LHR mRNA and accelerates its degradation. In response to preovulatory LH surge, the LH receptor expression in the ovary undergoes downregulation by accelerated degradation of LH receptor mRNA through the involvement of this RNA binding protein. Here we describe the intracellular mechanism triggered by LH/hCG (human chorionic gonadotropin) that leads to the regulated degradation of LH receptor mRNA. Downregulation of LH receptor mRNA was induced by treatment of cultured human granulosa cells with 10 IU of hCG. Activation of downstream target, extracellular signal-regulated protein kinase 1 and 2 (ERK 1/2) showed an increase within five min and sustained up to 1 h. Confocal analysis showed that ERK1/2 translocates to the nucleus after 15 min of hCG treatment. This leads to an increase in LRBP expression which then causes downregulation of LH receptor mRNA by accelerating its degradation. Treatment with UO126 or transfection with ERK specific siRNA (small interfering RNA) resulted in the abolishment of ERK activation as well as LHR mRNA downregulation. RNA electrophoretic mobility gel shift assay of the cytosolic fractions showed that hCG-induced increase in the LH receptor mRNA binding activity was also abrogated by these treatments. These results show that LH/hCG-induced LH receptor mRNA downregulation is initiated by the activation of ERK1/2 pathway by regulating the expression and activity of LH receptor mRNA binding activity.

Rol biológico y aplicaciones de los miRNAs en cáncer de seno / Biological role and applications of miRNAs in breast cancer

Los miRNAs son pequeños RNAs que participan en diversos procesos de regulación génica, mediante ribointerferencia y juegan un papel clave en diversos procesos biológicos, tales como proliferación celular, diferenciación y apoptosis. En consecuencia, la expresión alterada de miRNAs contribuye a la enfermedad humana, incluyendo cáncer. En esta revisión, nos centraremos en los recientes hallazgos de miRNAs que inciden en el desarrollo de cáncer y particularmente en cáncer de seno, simultáneamente evaluaremos sus mecanismos de regulación, su clasificación, su uso como marcadores de invasión tumoral, de sensibilidad a fármacos y adicionalmente exploraremos la utilidad de los miRNAs en el diagnóstico, seguimiento y tratamiento individualizo. Finalmente encontramos que los miRNAs representan una gran alternativa para entender las bases moleculares de los procesos tumorales implícitos en cáncer de seno y una vez se conozcan todas sus dianas, será posible dilucidar al menos en parte este proceso complejo y multigénico, ayudado mediante herramientas como la generación de bases de datos, para reportan la expresión diferencial de miRNAs, elementos que nos permitirá realizar medicina preventiva y mejorar la calidad de vida de los pacientes y sus familias.

MiRNAs are small RNAs that are involved in various processes of gene regulation by RNAi and play a key role in various biological, such as cell proliferation, differentiation and apoptosis processes. Consequently, the altered expression of miRNAs contribute to human disease, including cancer. In this review, we will focus on the recent findings of miRNAs that affect the development of cancer, particularly breast cancer, simultaneously evaluate their regulatory mechanisms , their classification , their use as markers of tumor invasion, drug susceptibility and further explore the utility of miRNAs in the diagnosis, monitoring and individualize treatment. Finally found that miRNAs represent a great alternative for understanding the molecular basis of implicit tumor processes in breast cancer and once all targets are known, it will be possible to elucidate at least in part this complex and multigenic process, aided by tools such as generation of databases, to report the differential expression of miRNAs, elements that allow us to preventive medicine and improve the quality of life of patients and their families.

Research advances in the miRNA regulation of autophagy / 中国肿瘤临床

MicroRNAs are endogenously expressed non-coding RNAs, which are composed of approximately 18 nucleotides to 25 nucleotides. Mature microRNAs regulate gene expression by base pairing with the 3'-untranslated region of target mRNAs. These mature microRNAs can degrade target mRNAs or inhibit translation. This process is a type of post-transcriptional regulation of gene ex-pression. Studies have shown that microRNAs are important in physiological and pathological processes, such as cell proliferation, cell differentiation, and cell death. This article provides an overview of the function of microRNAs in the regulation of macrophages.

Ribosome Profiling for Biomarker Discovery / 日本補完代替医療学会誌

It has been well known that protein level is estimated by the expression level of its mRNA. However, it is also argued that correlation between mRNA abundance and protein levels is weaker than previously thought. Recently a newly developed technique called ribosome profiling has drawn attention as a drastic countermeasure to improve the weak correlation. Here it is discussed that weak association of protein and mRNA levels seen in genome-wide analysis of gene expression such as microarray is attributable to post-transcriptional regulation including translational inhibition. This review further discusses how these issues are resolved by ribosome profiling and also addresses a possibility of biomarker discovery derived from this technique.<br>

Long non-coding RNA: Research progress / 第二军医大学学报

Long non-coding RNA (lncRNA) is a functional RNA segment longer than 200 nucleotides, with little or no protein-coding capacity. LncRNAs can regulate gene expression at epigenetic, transcription and post-transcription level, and widely participate in various physiological and pathological processes. More than one thousand lncRNAs have been found participating in the gene regulation of mammals. However, the functions and mechanism of lncRNA and its relation with disease remain poorly understood. This paper reviews the progress in lncRNA function study and the role of lncRNA in the development and progression of clinical disease.

Post-transcriptional Regulation of NK Cell Activation

Natural killer (NK) cells play key roles in innate and adaptive immune defenses. NK cell responses are mediated by two major mechanisms: the direct cytolysis of target cells, and immune regulation by production of various cytokines. Many previous reports show that the complex NK cell activation process requires de novo gene expression regulated at both transcriptional and post-transcriptional levels. Specialized un-translated regions (UTR) of mRNAs are the main mechanisms of post-transcriptional regulation. Analysis of post-transcriptional regulation is needed to clearly understand NK cell biology and, furthermore, harness the power of NK cells for therapeutic aims. This review summarizes the current understanding of mRNA metabolism during NK cell activation, focusing primarily on post-transcriptional regulation.

Research about the activity of CYP2A6 that related to regulative mechanism / 中国药理学通报

CYP2A6 is an important drug metabolic enzyme that plays a central role in pharmacology and toxicology.Coumarin and nicodine are mainly metabolized by it.CYP2A6 also have a close connection with diseases that related to smoking.While hnRNP A1 is a protein that shows an important regulative action on some specific genes at post-transcription level.Recently,researchers are paying more and more attention to the relationship between the activity of CYP2A6 and the expression of hnRNPA1.In order to master the change rule of CYP2A6 activity,we try to explain the regulative effect on CYP2A6 by hnRNP A1 at post-transcription level,which will bring an important effect on guiding clinical medicine treatments and smoking addictive therapy.

The mechanism of c-erbB-2 gene product increase in stomach cancer cell lines

c-erbB-2 oncogene encodes a growth factor receptor whose amino acid sequence has extensive homology with human epidermal growth factor receptor. It is frequently overexpressed in human breast, ovary, lung, and stomach cancers, where its overexpression is related significantly to the prognosis. Tl investigate the possible role of c-erbB-2 oncogene in the oncogenesis of stomach cancer, we examined the genetic alterations of c-erbB-2 oncogene in 4 stomach cancer cell lines, SNU-1, SNU-5, SNU-16 and KATO III. There were no differences in c-erbB-2 mRNA level as well as c-erbB-2 gene copy number among them. But gp185-erbB-2, c-erbB-2 gene product, was increased from 2- to 4-fold in SNU-1 and SNU-5 cells, compared with that in SNU-16 or KATO III cells. Our results suggest that post-transcriptional regulation of gp185erbB-2 expression may underlie gp185erbB-2 overexpression in cancer cells.