胃癌相关miRNA表达的表观遗传学调控机制

胃癌是人类最常见的肿瘤之一,其发病机制尚不完全清楚.微小RNA(microRNA,miRNA)是一组最近发现的长度为22个核苷酸左右的非编码RNA,具有负性调控基因表达的功能.本文对miRNA在胃癌发生中的作用及其表达调控机制进行综述.不断有文献显示,miRNA在多种肿瘤(包括胃癌)的发生过程中发挥着重要作用.作者和其他研究人员发现,miRNA的表达异常(如:miR-421和miR-21的上调或/和miR-31和miR-218的下调等)与胃癌的发生相关,提示miRNA是胃癌发生的重要因素.目前,miRNA表达的分子机制尚未完全明了.最近研究较清楚地显示,miRNA的表达受到DNA甲基化和组蛋白修饰等机制的调控.这说明,胃癌相关miRNA的表达水平受到表观遗传机制的调控。     

miR-21在皮肤相关疾病及创伤愈合中的作用

microRNA-21(miR-21)是一种内源性非编码RNA,在细胞增殖、分化过程中发挥了重要的调控作用。近年来，miR-21作为广泛研究的miRNA,其在皮肤相关疾病及创伤愈合中的作用备受关注。研究表明，miR-21作为一个“广泛因子”,通过抑制不同靶基因(PTEN、TIMP、PDCD4等)的转录翻译过程，影响不同细胞(角质形成细胞、T细胞、纤维细胞等)的增殖、凋亡、迁移和侵袭。同时，还能通过不同信号通路，促进炎症的发生，在皮肤肿瘤、皮肤免疫性疾病、皮肤炎症性疾病、皮肤创伤及瘢痕组织形成中发挥重要作用。本文回顾了miR-21在不同的皮肤疾病(黑色素瘤、皮肤鳞状细胞癌、T细胞淋巴瘤、银屑病、硬皮病等)和创伤愈合中的参与机制，旨在深化对miR-21分子在皮肤相关疾病和创伤愈合中的认识，表明miR-21除了有作为皮肤性疾病诊断的生物标志物潜力和评价药物疗效的能力外，更有望成为一种新型的治疗手段，为临床治疗难题提供新方向。     

microRNAs调控骨骼肌分化的分子机制

microRNA（miRNA）是一大类广泛存在于真核细胞当中的长度约22nt的内源性单链非编码RNA,通过与靶基因mRNA的3’非翻译区（3’untranslated region,3’UTR）结合在转录后水平调控靶基因的表达。miRNA作为调控基因表达的重要分子在骨骼肌分化调控中的作用越来越受到关注,阐明miRNA在骨骼肌增殖与分化中的作用机制具有重要的理论意义,同时也可为骨骼肌相关疾病的治疗提供新的思路。文章总结了miRNA,尤其是miR-1、miR-133和miR-206等肌肉特异性miRNA,在调控骨骼肌分化过程中作用机制的研究进展,以便于进一步工作的开展。     

果蝇微小RNA及其在衰老过程中的作用

微小RNA（microRNA, miRNA）是一类长度在22 nt左右的内源非编码小RNA,广泛存在于动物、植物、病毒等多种有机体中,是机体正常衰老与疾病的重要调控因子。本文对果蝇不同生长时期miRNA的表达模式、主要衰老相关信号通路以及与衰老相关的miRNA进行了综述。在果蝇的不同发育时期均有特定的miRNA发挥重要作用,其表达模式与功能相关;miRNA参与了主要衰老分子信号通路的调控,如胰岛素/胰岛素样生长因子（IIS）通路和雷帕霉素靶蛋白（TOR）通路。研究表明,miRNA通过调控衰老相关信号通路中的靶基因,进而促进或延缓果蝇衰老,如miR-34, miR-8, miR-14, miR let7和miR-277等。因此,研究参与衰老调控的miRNA,为阐明衰老机制及抗衰老药物的设计奠定了基础。     

microRNA-378 与相关疾病的研究进展

microRNAs是一类内源性表达的、长度约为22个核苷酸的非蛋白编码的单链RNA分子,是重要的转录后基因表达调控因子。在多种生理和病理过程中发挥重要作用,到目前为止,在动植物以及病毒中已经发现有24521个miRNA分子,miR-378是其中的一种,miR-378通过多种机制与众多疾病的发生发展密切相关。miR-378在不同肿瘤组织中起到不同作用,在胃癌,肝癌,结直肠癌等肿瘤中起到抑癌基因的作用,在白血病,胰腺癌,卵巢癌等肿瘤中起到癌基因的作用。在心血管方面,miR-378可以通过多种机制起到保护血管,延缓心血管疾病的发展。在骨代谢方面,miR-378可通过不同机制抑制或促进成骨细胞的分化。本文就其与肿瘤、心血管、骨代谢以及其他方面的研究进行介绍,为这些疾病的治疗和预防提供一种新的思路。     

涉及脂质代谢的miRNA及其对动脉粥样硬化发展和治疗的进展

MicroRNA是一类长度为18～24碱基的非编码小分子RNA,作为基因表达转录后调控因子,涉及多种生理、病理过程,包括调节脂质代谢和动脉粥样硬化。通过机体代谢,miR-126、miR-155、miR-221/222、miR-124、miR-145、miR-133、miR-663、miR-29等可参与动脉粥样硬化的形成和发展。目前有超过30种miRNA,包括miR-33、miR-122、miR-223和miR-27a/b也在调节脂肪酸生物合成及氧化,胆固醇的流出等脂质代谢中起重要作用。此外,"循环miRNA"的发现为其成为动脉粥样硬化性疾病的新型生物标志物提供可能。本综述通过探讨miRNA调节脂质代谢途径,参与动脉粥样硬化的发生、发展过程,为动脉粥样硬化疾病提供新的分子学观点并为深入研究其治疗靶点提供理论依据。     

MicroRNAs与疾病和发育

作为模式生物实验系统,线虫可用于研究控制动物发育和人类疾病遗传机制。研究发育缺陷的线虫突变体有助于在动物中发现对发育和生理过程有重要调控作用的基因。其中一些基因编码一类小RNA,如microRNA(miRNA),通过作用于特定基因信使RNA来调控其蛋白质表达。一些在线虫发育过程中有功能的miRNA在人体中也存在。它们参与调控与疾病相关的生物学过程,如癌症、糖尿病和神经退行性疾病。通过分析miRNA在临床样品、哺乳动物细胞和模式生物线虫中的表达,从而揭示miRNA调控途径在相关人类疾病中的功能。     

反义抑制和过表达miR-219引起斑马鱼胚胎发育异常

业已表明,miRNA在转录后水平对基因表达起调控作用,参与诸多重要的生理、病理过程。本研究利用整体原位杂交和Northern杂交技术发现miR-219主要从16体节期开始在中后脑和脊髓表达。在此基础上,采用基因沉默和过表达技术观察到斑马鱼受精卵在显微注射miR-219和反义miR-219后均导致其胚胎发育缺陷。进一步研究表明,miR-219过表达可以诱导胚胎细胞凋亡。我们的初步结果为深入研究miR-219在胚胎发育过程中的调控机制提供了基础。     

MiR-148生物学功能研究进展*

microRNA(miRNA)是一种分布广泛、功能多样、在物种间高度保守的非编码单链RNA。miRNA可通过与目标mRNA的3'非编码区(3'UTR)完全或不完全靶向结合来调控基因的表达,在转录水平发挥调控作用。miRNA以稳定的形式存在于各种体液中,可作为不同生理或病理状态下的生物标志物。基于前期高通量测序发现miR-148在猪初乳与常乳外泌体中差异表达,拟从免疫、肿瘤及其他生物学功能,综述miR-148相关研究进展,以期为乳汁外泌体运载miR-148发挥生物学功能的研究提供参考。     

MiRNA对上皮-间质转化的调控作用

上皮-间质转化(epithelial-mesenchymal transition,EMT)是胚胎发育、组织分化和器官形成的重要生理过程,也是慢性炎症、器官纤维化和癌症转移等疾病的重要病理过程。近年来发现多种微RNA(microRNA,miRNA)通过靶向EMT相关蛋白,例如E-钙粘蛋白(E-cadherin)、波形蛋白(Vimentin)、Snail、ZEB和Twist等转录因子来调控EMT的发生和发展,这些例子揭示了EMT分子机制的"冰山一角",一个庞大的EMT转录后调控网络正在被发现。本文总结了miRNA对EMT相关蛋白的调控作用,并对miRNA-EMT调控网络的后续研究进行了讨论。     

MiRNA在特发性肺纤维化中的作用

近年来研究发现微RNA（microRNA,miRNA）与机体人部分生理、病理过程均有密切关系,如：组织的发育和分化、组织再生、病毒防御以及细胞增殖与凋亡等。miRNA在特发性肺纤维化（IPF）中的作用也日渐为研究者所重视,在IPF中有些miRNA上调（如miR-155、miR-21）,有些下调（如let-7、miR-29、miR-200）。这一发现为寻找IPF治疗方法提供了一个新的突破口。本文对近年来miRNA在IPF中作用的研究进展进行了综述,并对miRNA-21、let-7d、miRNA-155、miRNA-29以及miRNA-200在肺纤维化中的作用分别进行了阐述,为研究miRNA征IPF中的作用及机制提供一定参考。     

miR-203 Acts as a Tumor Suppressor Gene in Osteosarcoma by Regulating RAB22A

microRNAs (miRNAs), small noncoding RNAs of 19–25 nt, play an important roles in the pathological processes of tumorigenesis. The object of this study was to study the expression and function of miR-203 and to found its target gene in osteosarcoma. In our study, we found the expression level of miR-203 was significantly downregulated in osteosarcoma cell lines and tissues. In addition, overexpression of miR-203 inhibited the osteosarcoma cell proliferation and migration and inhibited Mesenchymal-to-Epithelial reversion Transition (MErT). Moreover, we identified RAB22A as a direct target of miR-203 and RAB22A overexpression blocks the roles of miR-203 in osteosarcoma cell. Furthermore, we demonstrated that RAB22A expression was upregulated in human osteosarcoma cell lines and tissues. Take together, our results demonstrated that miR-203 act as a tumor suppressor miRNA through regulating RAB22A expression and suggested its involvement in osteosarcoma progression and carcinogenesis.     

miR-155 gene: A typical multifunctional microRNA

In the last years small RNA molecules, i.e. microRNA (miRNA) encoded by miR genes, have been found to play a crucial role in regulating gene expression of a considerable part of plant's and animal's genome. Here, we report the essential information on biogenesis of miRNAs and recent evidence on their important role in human diseases. Emphasis has been given to miR-155, since this molecule represents a typical multifunctional miRNA. Recent data indicate that miR-155 has distinct expression profiles and plays a crucial role in various physiological and pathological processes such as haematopoietic lineage differentiation, immunity, inflammation, cancer, and cardiovascular diseases. Moreover, miR-155 has been found to be implicated in viral infections, particularly in those caused by DNA viruses. The available experimental evidence indicating that miR-155 is over expressed in a variety of malignant tumors allows us to include this miRNA in the list of genes of paramount importance in cancer diagnosis and prognosis. Exogenous molecular control in vivo of miR-155 expression could open up new ways to restrain malignant growth and viral infections, or to attenuate the progression of cardiovascular diseases.     

Distinguishing Tumor and Stromal Sources of MicroRNAs Linked to Metastasis in Cutaneous Melanoma

MicroRNA (miRNA) dysregulation in cancer causes changes in gene expression programs regulating tumor progression and metastasis. Candidate metastasis suppressor miRNA are often identified by differential expression in primary tumors compared to metastases. Here, we performed comprehensive analysis of miRNA expression in The Cancer Genome Atlas (TCGA) skin cutaneous melanoma (SKCM) tumors (97 primary, 350 metastatic), and identified candidate metastasis-suppressor miRNAs. Differential expression analysis revealed miRNA significantly downregulated in metastatic tumors, including miR-205, miR-203, miR-200a-c, and miR-141. Furthermore, sequential feature selection and classification analysis identified miR-205 and miR-203 as the miRNA best able to discriminate between primary and metastatic tumors. However, cell-type enrichment analysis revealed that gene expression signatures for epithelial cells, including keratinocytes and sebocytes, were present in primary tumors and significantly correlated with expression of the candidate metastasis-suppressor miRNA. Examination of miRNA expression in cell lines revealed that candidate metastasis-suppressor miRNA identified in the SKCM tumors, were largely absent in melanoma cells or melanocytes, and highly restricted to keratinocytes and other epithelial cell types. Indeed, the differences in stromal cell composition between primary and metastatic tumor tissues is the main basis for identification of differential miRNA that were previously classified as metastasis-suppressor miRNAs. We conclude that future studies must consider tumor-intrinsic and stromal sources of miRNA in their workflow to identify bone fide metastasis-suppressor miRNA in cutaneous melanoma and other cancers.     

miR-203 accelerates apoptosis and inflammation induced by LPS via targeting NFIL3 in cardiomyocytes

Myocarditis is an inflammatory disease of the myocardium. MicroRNA-203 (miR-203) is involved in various physiological and pathological processes. In this work, we aimed to explore the roles and potential mechanisms of miR-203 in myocarditis in vitro. Cardiomyocyte H9c2 was subjected to 10 μg/mL lipopolysaccharide (LPS) for 24 hours. Real-time polymerase chain reaction analysis revealed that LPS upregulated miR-203 expression in H9c2 cells. Cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) assays demonstrated that inhibition of miR-203 reduced cell injury induced by LPS. The cell apoptosis rate, caspase 3 activity, caspase 3/7 activities, and the expression of cleaved-caspase 3 (c-caspase 3) were declined upon miR-203 depletion. In addition, miR-203 silencing attenuated the expression and production of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-6, and IL-8). On the contrary, overexpression of miR-203 showed the opposite trend in cell apoptosis and inflammation. Luciferase reporter assay confirmed that miR-203 could bind with the nuclear factor interleukin-3 (NFIL3) 3′-untranslated regions (3′-UTR), and miR-203 regulated the expression of NFIL3 negatively. Moreover, NFIL3 silencing partly abolished the myocardial protective functions of miR-203 inhibitor. Herein, we suggest that miR-203 promoted cell apoptosis and inflammation induced by LPS via targeting NFIL3.     

MicroRNA-203 reinforces stemness properties in melanoma and augments tumorigenesis in vivo

One of the challenges encountered in microRNA (miRNA) studies is to observe their dual role in different conditions and cells. This leads to a tougher prediction of their behavior as gene expression regulators. miR-203 has been identified to play a negative role in the progression of malignant melanoma; however, it has been reported, with dual effect, as both an oncomiR and tumor suppressor miRNA in some malignancies, such as breast cancer, meanwhile, the role of miR-203 in melanoma stem cells or even metastatic cells is unclear. In the present study, after observation of upregulation of miR-203 in melanoma patient's serum and also melanospheres as cancer stem cells model, we examined its overexpression on the stemness potential and migration ability of melanoma cells. Our data demonstrated that the increased miR-203 level was significantly associated with significant increase in the ability of proliferation, colony and spheres formation, migration, and tumorigenesis in A375 and NA8 cells. All of these changes were associated with enhancement of BRAF, several epithelial to mesenchymal transition factors, and stemness genes. In conclusion, our results clearly determined that miR-203 could be down-regulateddownregulated in melanoma tissues but be overexpressed in melanoma stem cells. It has an important role as oncomiR and promote repopulation, tumorigenicity, self-renewal, and migration. Therefore, we suggested overexpression of miR-203 as biomarker for early detection of metastasis. However, more studies are needed to validate our data.