The roles of microRNA in cancer and apoptosis

microRNAs (miRNAs) are highly conserved, non-protein-coding RNAs that function to regulate gene expression. In mammals this regulation is primarily carried out by repression of translation. miRNAs play important roles in homeostatic processes such as development, cell proliferation and cell death. Recently the dysregulation of miRNAs has been linked to cancer initiation and progression, indicating that miRNAs may play roles as tumour suppressor genes or oncogenes. The role of miRNAs in apoptosis is not fully understood, however, evidence is mounting that miRNAs are important in this process. The dysregulation of miRNAs involved in apoptosis may provide a mechanism for cancer development and resistance to cancer therapy. This review examines the biosynthesis of miRNA, the mechanisms of miRNA target regulation and the involvement of miRNAs in the initiation and progression of human cancer. It will include miRNAs involved in apoptosis, specifically those miRNAs involved in the regulation of apoptotic pathways and tumour suppressor/oncogene networks. It will also consider emerging evidence supporting a role for miRNAs in modulating sensitivity to anti-cancer therapy.     

植物MEP途径的代谢调控机制

萜类代谢途径是植物中最重要的次生代谢途径之一,对其有效的调控决定着植物的生长发育、抗性及品质等各个方面。植物中类萜合成的前体物在质体中是由2-C-甲基-D-赤藓糖醇-4-磷酸(2-C-Methyl-D-Erythritol-4-Phosphate,MEP)途径合成的,MEP途径中的许多基因除了受到多基因编码和转录水平的调节外,还受到转录后调节机制的调节,而转录后调节是一种新发现的调节方式,其机制还不是很清楚。该文重点对近年来国内外有关植物MEP途径的多种调节方式,尤其是转录后调节的调节机制及其可能参与的信号分子方面的研究进展进行综述,为植物的MEP途径的代谢调控提供参考。     

Krüppel样因子在肌肉组织中的功能研究进展

Krüppel样因子(Krüppel-like factors, KLFs)是一类C-末端含有3个C₂H₂锌指结构的转录因子,N-末端为转录调控结构域,能够结合多种特异蛋白质,介导转录调控。目前在人体基因组中共发现18种KLFs,它们在多种类型人类细胞的分化、表型维持和生理功能调控中发挥重要作用。多个KLFs参与了对人和动物的心肌、平滑肌和骨骼肌的发育和功能的调控。在心肌中,KLF4、KLF10、KLF11和KLF15参与心肌肥大的负调控,KLF6参与调控心脏纤维化,KLF13调控胚胎时期的心肌发育。在血管平滑肌中,KLF4受促增殖或促分化因子调控,介导调控血管平滑肌表型转换;KLF5促进血管平滑肌增殖,KLF8和KLF15抑制血管平滑肌增殖。在骨骼肌中,KLF2、KLF3、KLF4、KLF10和KLF15调控骨骼肌发育,此外,KLF15是肌肉组织能量代谢的调节因子。本文综述了KLFs在心肌、平滑肌和骨骼肌中的功能研究进展,为进一步揭示KLFs在肌肉组织中的作用和肌肉相关疾病的分子机制提供参考。     

Adaptive,or stationary-phase,mutagenesis, a component of bacterial differentiation in Bacillus subtilis

Adaptive (stationary-phase) mutagenesis occurs in the gram-positive bacterium Bacillus subtilis. Furthermore, taking advantage of B. subtilis as a paradigm for the study of prokaryotic differentiation and development, we have shown that this type of mutagenesis is subject to regulation involving at least two of the genes that are involved in the regulation of post-exponential phase prokaryotic differentiation, i.e., comA and comK. On the other hand, a functional RecA protein was not required for this type of mutagenesis. The results seem to suggest that a small subpopulation(s) of the culture is involved in adaptive mutagenesis and that this subpopulation(s) is hypermutable. The existence of such a hypermutable subpopulation(s) raises important considerations with respect to evolution, the development of specific mutations, the nature of bacterial populations, and the level of communication among bacteria in an ecological niche.     

肌肉生长抑制素对脂肪细胞生长发育和脂代谢的调控

肌肉生长抑制素(MSTN)对骨骼肌生长的抑制作用已得到证实,但其调控脂肪组织的作用还不是十分清楚。本文综述了MSTN调控脂肪细胞生长发育和脂代谢的相关机制和可能研究趋势。     

On the transition from the meiotic to mitotic cell cycle during early mouse development

Here, we outline the mechanisms involved in the regulation of cell divisions during oocyte maturation and early cleavages of the mouse embryo. Our interest is focused on the regulation of meiotic M-phases and the first embryonic mitoses that are differently tuned and are characterized by specifically modified mechanisms, some of which have been recently identified. The transitions between the M-phases during this period of development, as well as associated changes in their regulation, are of key importance for both the meiotic maturation of oocytes and the further development of the mammalian embryo. The mouse is an excellent model for studies of the cell cycle during oogenesis and early development. Nevertheless, a number of molecular mechanisms described here were discovered or confirmed during the study of other species and apply also to other mammals including humans.     

乳腺发育及泌乳相关miRNA研究进展

MicroRNA(miRNA)是一种重要的转录后调控的非编码RNA, 参与调控哺乳动物乳腺发育和泌乳。文章总结了乳腺发育和泌乳过程中miRNA表达的时空特异性, 综述了个别miRNA对乳腺发育和泌乳的调节作用, 旨在为乳腺miRNA的研究提供指导, 为利用miRNA促进乳腺健康发育和调控高质高效产乳提供理论基础和研究思路。     

Signaling molecules involved in the transition of growth to development of Dictyostelium discoideum

The social amoeba Dictyostelium discoideum, a powerful paradigm provides clear insights into the regulation of growth and development. In addition to possessing complex individual cellular functions like a unicellular eukaryote, D. discoideum cells face the challenge of multicellular development. D. discoideum undergoes a relatively simple differentiation process mainly by cAMP mediated pathway. Despite this relative simplicity, the regulatory signaling pathways are as complex as those seen in metazoan development. However, the introduction of restriction-enzyme-mediated integration (REMI) technique to produce developmental gene knockouts has provided novel insights into the discovery of signaling molecules and their role in D. discoideum development. Cell cycle phase is an important aspect for differentiation of D. discoideum, as cells must reach a specific stage to enter into developmental phase and specific cell cycle regulators are involved in arresting growth phase genes and inducing the developmental genes. In this review, we present an overview of the signaling molecules involved in the regulation of growth to differentiation transition (GDT), molecular mechanism of early developmental events leading to generation of cAMP signal and components of cAMP relay system that operate in this paradigm.     

The protein tyrosine phosphatase PTP-Basophil/Basophil-like. Interacting proteins and molecular functions.

The protein tyrosine phosphatase PTP-Basophil (PTP-Bas) and its mouse homologue, PTP-Basophil-like (PTP-BL), are high molecular mass protein phosphatases consisting of a number of diverse protein-protein interaction modules. Several splicing variants of these phosphatases are known to exist thus demonstrating the complexity of these molecules. PTP-Bas/BL serves as a central scaffolding protein facilitating the assembly of a multiplicity of different proteins mainly via five different PDZ domains. Many of these interacting proteins are implicated in the regulation of the actin cytoskeleton. However, some proteins demonstrate a nuclear function of this protein tyrosine phosphatase. PTP-Bas is involved in the regulation of cell surface expression of the cell death receptor, Fas. Moreover, it is a negative regulator of ephrinB phosphorylation, a receptor playing an important role during development. The phosphorylation status of other proteins such as RIL, IkappaBalpha and beta-catenin can also be regulated by this phosphatase. Finally, PTP-BL has been shown to be involved in the regulation of cytokinesis, the last step in cell division. Although the precise molecular function of PTP-Bas/BL is still elusive, current data suggest clearly that PTP-Bas/BL belongs to the family of PDZ domain containing proteins involved in the regulation of the cytoskeleton and of intracellular vesicular transport processes.     

棉纤维发育及其相关基因表达调控研究进展

棉纤维的强度和长度是评价棉花品质优劣的重要标准。棉纤维发育是一个高度程序化的调控过程。在纤维发育的各个时期,均有大量基因参与纤维细胞发育的调控。本文介绍棉纤维细胞发育各个时期的形态结构和生理生化特征以及一些纤维特异性基因表达调控等方面的研究概况和最新进展,以期能够在细胞和分子水平上了解棉纤维发育的基本生物学过程及其调控机制。     

棉纤维发育及其相关基因表达调控研究进展

棉纤维的强度和长度是评价棉花品质优劣的重要标准。棉纤维发育是一个高度程序化的调控过程。在纤维发育的各个时期, 均有大量基因参与纤维细胞发育的调控。本文介绍棉纤维细胞发育各个时期的形态结构和生理生化特征以及一些纤维特异性基因表达调控等方面的研究概况和最新进展, 以期能够在细胞和分子水平上了解棉纤维发育的基本生物学过程及其调控机制。     

GAMYB controls different sets of genes and is differentially regulated by microRNA in aleurone cells and anthers

GAMYB is a component of gibberellin (GA) signaling in cereal aleurone cells, and has an important role in flower development. However, it is unclear how GAMYB function is regulated. We examined the involvement of a microRNA, miR159, in the regulation of GAMYB expression in cereal aleurone cells and flower development. In aleurone cells, no miR159 expression was observed with or without GA treatment, suggesting that miR159 is not involved in the regulation of GAMYB and GAMYB-like genes in this tissue. miR159 was expressed in tissues other than aleurone, and miR159 over-expressors showed similar but more severe phenotypes than the gamyb mutant. GAMYB and GAMYB-like genes are co-expressed with miR159 in anthers, and the mRNA levels for GAMYB and GAMYB-like genes are negatively correlated with miR159 levels during anther development. Thus, OsGAMYB and OsGAMYB-like genes are regulated by miR159 in flowers. A microarray analysis revealed that OsGAMYB and its upstream regulator SLR1 are involved in the regulation of almost all GA-mediated gene expression in rice aleurone cells. Moreover, different sets of genes are regulated by GAMYB in aleurone cells and anthers. GAMYB binds directly to promoter regions of its target genes in anthers as well as aleurone cells. Based on these observations, we suggest that the regulation of GAMYB expression and GAMYB function are different in aleurone cells and flowers in rice.     

Heterotrimeric G protein signaling in cancer cells with regard to metastasis formation

The signal transduction mediated by heterotrimeric G proteins is involved in the regulation of a plethora of cell functions ranging from the sensation of light, taste and odor to chemotaxis, inflammation and the coordination of immune responses. These reactions have in common that they occur fast and are short-lived. Apart from this, it becomes increasingly evident, that the signaling of heterotrimeric G proteins has an imminent function in gene regulation, too, and therefore mediates even long-term effects. Herein, we illustrate the pathways of the four classes of α subunits and of the βγ subunits of these heterotrimeric G proteins especially with regard to their function in cancer. G protein signaling is crucial for the development and localization of metastases and furthermore has been shown to be involved in tumor growth and angiogenesis. We summarize the current knowledge, how these processes are regulated by the short-term cellular response and the long-term gene regulation in cancer cells, and we discuss possible strategies for a therapeutic intervention.     

SAHA Inhibits Somatic Hyperalgesia Induced by Stress Combined with Orofacial Inflammation Through Targeting Different Spinal 5-HT Receptor Subtypes

Neurochemical Research - Epigenetic regulation of gene expression has been implicated in the development of chronic pain. However, little is known about whether this regulation is involved in the...     

Sphingosine-1-phosphate lyase in development and disease: sphingolipid metabolism takes flight

Sphingosine-1-phosphate lyase (SPL) is a highly conserved enzyme that catalyses the final step of sphingolipid degradation, namely the irreversible cleavage of the carbon chain at positions 2-3 of a long-chain base phosphate (LCBP), thereby yielding a long-chain aldehyde and phosphoethanolamine. LCBPs are potent signaling molecules involved in cell proliferation, survival, migration, cell-cell interactions and cell stress responses. Therefore, tight regulation of LCBP signaling is required for proper cell function, and perturbations of this system can lead to alterations in biological processes including development, reproduction and physiology. SPL is a key enzyme in regulating the intracellular and circulating levels of LCBPs and is, therefore, gaining attention as a putative target for pharmacological intervention. This review provides an overview of our current understanding of SPL structure and function, mechanisms involved in SPL regulation and the role of SPL in development and disease.     

The multifunctional role of fibroblasts during wound healing in Hirudo medicinalis (Annelida, Hirudinea)

Extracellular matrix components play a key role during the angiogenic process for a correct development of blood vessels: fibroblasts are the main cell type involved in the regulation of ECM protein production. In this study we characterize H. medicinalis fibroblasts and demonstrate that they take part to the regulation of angiogenesis that occurs during wound healing process. Massive proliferation and phenotypic modification are two distinctive markers of fibroblast activation. These cells, that are usually responsible for collagen production and function as an energy reservoir, are recruited during wound healing to form a collagen scaffold through a direct mechanic action and through secretion of specific proteoglycans. In addition we show that the activity of fibroblasts is modulated by EGF, a growth factor involved in wound healing in vertebrates. The formation of bundles of collagen fibrils by fibroblasts is fundamental for the development and migration of new blood vessels in lesioned areas during wound repair: administration of lovastatin in explanted leeches affects fibroblasts, damages collagen "scaffold" and indirectly causes the reduction of neo-capillary formation.     

Protein kinase C isoforms and lipid second messengers: a critical nuclear partnership?

A growing body of evidence, accumulated over the past 15 years, has highlighted that the protein kinase C family of isozymes is capable of translocating to the nucleus or is resident within the nucleus. The comprehension of protein kinase C isoform regulation within this organelle is under development. At present, it is emerging that lipid second messengers may play at least two roles in the control of nuclear protein kinase C: on one side they serve as chemical attractants, on the other they directly modulate the activity of specific isoforms. One of the best characterized lipid second messenger that could be involved in the regulation of nuclear PKC activity is DAG. The existence of two separate pools of nuclear DAG suggests that this lipid second messenger might be involved in distinct pathways that lead to different cell responses. Nuclear phosphatidylglycerol, D-3 phosphorylated inositol lipids and nuclear fatty acids are involved in a striking variety of critical biological functions which may act by specific PKC activation. The fine tuning of PKC regulation in cells subjected to proliferating or differentiating stimuli, might prove to be of great interest also for cancer therapy, given the fact that PKC-dependent signaling pathways are increasingly being seen as possible pharmacological target in some forms of neoplastic diseases. In this article, we review the current knowledge about lipid second messengers that are involved in regulating the translocation and/or the activity of different protein kinase C isoforms identified at the nuclear level.