微小RNA-203与肿瘤

微小RNA (miR)-203具有细胞干性抑制潜能,可通过抑制细胞干性相关转录因子的表达来调节细胞上皮样分化.研究表明miR-203在多种肿瘤组织中表达异常,包括膀胱癌、乳腺癌、结肠癌和胰腺癌等.miR-203通过调节细胞增殖、分化和凋亡在肿瘤的发生发展中发挥重要作用.     

微小RNA-30a:肿瘤治疗的潜在靶点

微小RNA(miRNA)是长约20~25个核苷酸的内源性非编码RNA,主要通过抑制mRNA翻译和诱导mRNA降解而调节靶基因的表达,人类大约30%的基因受miRNAs调节。研究发现,大量miRNAs在肿瘤中表达失调,常常引起多种重要过程的紊乱,包括细胞增殖、侵袭与转移、凋亡以及耐药等。在肿瘤的发生过程中,不同的miRNA可能起着类似抑癌基因或者癌基因的作用,参与调节肿瘤细胞发生、发展等过程。miR-30a是miRNA的成员之一,通过调节靶基因的表达,参与调控肿瘤细胞增殖、转移和凋亡等过程。不同肿瘤血清中miR-30a的表达水平对肿瘤的早期诊断、治疗以及预后判断有着重要作用。此外,miR-30a的表达失调还与抗肿瘤药物耐药性的产生密切相关,推测其有望成为肿瘤治疗的一个潜在新靶标。本文就近年来miR-30a在肿瘤中作用的最新研究进展作一综述。     

微小RNA-494在肿瘤发生发展中的作用

微小RNA-494 (miR-494)参与正常细胞的细胞周期调控、分化和凋亡等过程.近年来研究表明,miR-494的异常表达与肿瘤的发生密切相关,其参与肿瘤细胞的侵袭和转移等过程.miR-494是一种肿瘤抑制基因,也可作为癌基因,其通过多种靶基因、信号通路对肿瘤发生发展进行调控.     

微小RNA在肿瘤基因中的研究进展

微小RNA(miRNA)是近年来发现的一类长度为19～25碱基的非编码小分子单链RNA,普遍存在于生物界,在不同物种间具有高度的保守性,其表达具有细胞特异性或组织特异性.通过与miRNA特异性的碱基完全或不完全的互补配对,降解其靶基因miRNA或抑制其翻译,从而参与肿瘤细胞的增殖、分化和细胞凋亡过程.miRNA可通过调控其靶基因,影响肿瘤的发生和发展,发挥着类似于癌基因或抑癌基因的功能.目前研究表明,miRNA与肿瘤的发生相关.阐明miRNA与肿瘤基因的关系,对其作为癌症潜在的治疗靶点具有重要意义.     

微小RNA-10b在肿瘤发生发展中的作用

微小RNA(miRNA)是一类广泛存在于真核生物中的非编码单链小分子RNA,长度为19~25个核苷酸(nt),可在转录后调控基因的表达。miRNA-10b长度为23 nt,基因位于人类2号染色体短臂3区1带1亚带同源异型盒D基因簇(HOXD)中,靠近HOXD4基因。近年来,越来越多的研究指出,miRNA-10b通过靶向抑制HOXD10、细胞黏附分子1(CADM1)、磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α(PIK3CA)、磷酸酶和张力蛋白同源基因(PTEN)和过氧化物酶体增殖物激活受体γ(PPARγ)等与细胞凋亡、增殖、迁移和侵袭相关的基因,在多种肿瘤的发生发展中扮演着重要的角色。本文就miRNA-10b在肿瘤发生发展中的作用及其分子机制的研究进展作一综述。     

miR-21与肿瘤研究进展

目的:总结国内外关于miR-21与肿瘤发生机制、肿瘤诊断、治疗、预后的研究进展。方法:以"microRNA、miR-21、肿瘤和靶基因"为关键词,应用PubMed及CNKI期刊全文数据库检索系统,检索2000-01-2011-11的相关文献,共检索到英文文献126篇,中文文献62篇。纳入标准:1)miR-21在肿瘤发生发展中的作用机制;2)miR-21已证实的部分靶基因的功能;3)miR-21在肿瘤的诊断、治疗和预后中的作用。排除与本研究无关的文献,最终纳入分析29篇文献。结果:miR-21的基因定位决定了其与肿瘤的发生发展密切相关;部分靶基因如pdcd4、pten和tpm1参与肿瘤细胞的增殖、分化和凋亡、血管浸润和转移等生物学过程,因此检测miR-21表达变化可作为肿瘤诊断、治疗和预后的重要生物学指标。结论:miR-21与多种肿瘤的发生发展密切相关,未来可作为肿瘤诊断,治疗和预后的重要生物学指标。     

miR-149与肿瘤关系的研究进展

miRNAs是一类长度约为20~25个核苷酸,参与基因调控表达的内源性非编码RNA。miR-149作为miRNAs的重要成员,在多种肿瘤中表达异常,其表达水平与肿瘤细胞增殖、转移、凋亡、耐药、患者的早期诊断及预后密切相关。因此,miR-149有望成为新一类抗肿瘤治疗的靶点。     

微RNA-106b～25基因簇在肿瘤中的研究进展

微RNA(miRNA)-106b～25基因簇由miR-106b、miR-93及miR-25组成,与miR-17～92原癌基因簇有着极高的同源性.已有的研究表明,该簇miRNA成员在多种肿瘤中高表达.这些miR通过抑制细胞周期抑制因子p21、p57及凋亡抑制因子Bim来促进肿瘤细胞增殖,抑制细胞凋亡.在转化生长因子β(T...     

微小RNA-449在肿瘤中的作用及其调控机制

超过50％的微小RNA (miRNA)定位于肿瘤相关的基因组扩增区域或脆性位点,可具有癌基因或抑癌基因的功能.近年来研究显示,在人类胃癌、肺癌、卵巢癌等恶性肿瘤中miR-449表达降低,被认为是一个抑癌miRNA.miR-449表达异常可能与肿瘤的发生和发展过程密切相关,研究其功能及调控机制,可为肿瘤诊断、治疗和预后判断提供重要线索.     

微小RNA-296在肿瘤演进中的作用

肿瘤演进是一个多步骤、多因素参与的复杂过程.微小RNA-296(miR-296)在肿瘤演进中扮演重要角色,涉及肿瘤细胞的增殖、分化、血管新生、侵袭、迁移、凋亡以及耐药性等一系列过程.     

MircoRNA-26a与肿瘤

微小RNA(microRNAs,miRNAs)是一类由20个-22个核苷酸组成的小片段非编码RNA,通过靶向结合基因mRNA的3'非翻译区(3'-UTR)调控其表达.许多研究报道miRNAs参与肿瘤的发生发展.MiR-26a在不同的肿瘤中发挥不同的作用,在肿瘤增殖、转移侵袭、血管形成、生物代谢及诊断预后中都有作用.本文就miR-26a与肿瘤关系的研究进展进行综述.     

MicroRNA-320a inhibits proliferation and invasion of breast cancer cells by targeting RAB11A

MicroRNAs (miRNAs) are deregulated in many types of cancer including breast cancer (BC). miR-320a dysregulation has been associated with different malignancies although its prognostic significance remains unclear. Here, we examined the role of miR-320a in BC and explored the underlying mechanisms. Our results showed that miR-320a was significantly downregulated in BC cell lines and tissues, and its ectopic expression inhibited cell proliferation, migration, and invasion in vitro and tumor growth in a mouse xenograft model. We identified Rab11a as a direct target of miR-320a and showed that its expression was upregulated in tumor samples and inversely correlated with the expression of miR-320a. In BC cells, the downregulation of Rab11a through miR-320a was concomitant with the inactivation of Akt. Overexpression of Rab11a abrogated miR-320a-induced inhibition of BC growth and invasion. These results suggest that miR-320a may act as a tumor suppressor in BC through a mechanism involving the modulation of Rab11a expression and the activation of the Akt signaling pathway. miR-320a may therefore serve as a biomarker for BC, and the modulation of its expression may represent a novel therapeutic strategy in BC treatment.     

MicroRNA-320c inhibits tumorous behaviors of bladder cancer by targeting Cyclin-dependent kinase 6

Background

Increasing evidence has suggested that dysregulation of microRNAs (miRNAs) could contribute to human disease including cancer. Previous miRNA microarray analysis illustrated that miR-320c is down-regulated in various cancers. However, the roles of miR-320c in human bladder cancer have not been well elucidated. Therefore, this study was performed to investigate the biological functions and molecular mechanisms of miR-320c in human bladder cancer cell lines, discussing whether it could be a therapeutic biomarker of bladder cancer in the future.

Methods

Two human bladder cancer cell lines and samples from thirteen patients with bladder cancer were analyzed for the expression of miR-320c by quantitative RT-PCR. Over-expression of miR-320c was established by transfecting mimics into T24 and UM-UC-3. Cell proliferation and cell cycle were assessed by cell viability assay, flow cytometry and colony formation assay. Cell motility ability was evaluated by transwell assay. The target gene of miR-320c was determined by luciferase assay, quantitative RT-PCR and western blot. The regulation of cell cycle and mobility by miR-320c was analyzed by western blot.

Results

We observed that miR-320c was down-regulated in human bladder cancer tissues and bladder cancer cell lines T24 and UM-UC-3. Over-expression of miR-320c could induce G1 phase arrest in UM-UC-3 and T24 cells, and subsequently inhibited cell growth. We also indentified miR-320c could impair UM-UC-3 and T24 cell motility. In addition, we identified CDK6, a cell cycle regulator, as a novel target of miR-320c. Moreover, we demonstrated miR-320c could induce bladder cancer cell cycle arrest and mobility via regulating CDK6. We also observed that inhibition of miR-320c or restoration of CDK6 in miR-320c-over-expressed bladder cancer cells partly reversed the suppressive effects of miR-320c.

Conclusions

miR-320c could inhibit the proliferation, migration and invasion of bladder cancer cells via regulating CDK6. Our study revealed that miR-320c could be a therapeutic biomarker of bladder cancer in the future.     

MicroRNA-135在肿瘤中的研究进展

MircroRNA（miRNAs）通过与信使RNA（mRNA）的序列互补来降解靶mRNA并抑制蛋白质翻译,在细胞增殖、分化、发育和凋亡等方面起着重要的作用。许多miRNA可作为原癌基因或抑癌基因,在肿瘤的发生和发展中发挥重要作用。越来越多的研究表明,微miR-135（miR-135）与肿瘤的发生发展密切相关,本文主要对近年来miR-135参与调节肿瘤细胞增殖、凋亡、侵袭、转移、耐药和预后等方面的机制作一综述,期望能对肿瘤的早期诊断、治疗和预后判断有所帮助。     

MicroRNA-19a and -19b regulate cervical carcinoma cell proliferation and invasion by targeting CUL5

MicroRNAs (miRNAs) play a key role in the regulation of gene expression. In this study, we demonstrate that microRNA-19a and -19b (miR-19a/b) are highly expressed in human cervical cancer cells and are involved in maintaining the malignant phenotypes of HeLa and C33A cells. Up-regulation of miR-19a and miR-19b promoted cell growth and invasion, whereas knockdown of miR-19a and miR-19b yielded the reverse phenotype. CUL5 was identified as a novel target gene of both miR-19a and miR-19b. CUL5 ectopic over-expression without its 3' untranslated region (UTR) abolished the effect of miR-19a/b on HeLa and C33A cell proliferation and invasion. These results indicated that miR-19a/b directly and negatively regulate CUL5 expression in cervical cancer cells, highlighting the importance of miR-19a and miR-19b and their target genes in tumorigenesis.     

miR-320c regulates gemcitabine-resistance in pancreatic cancer via SMARCC1

Background:

Gemcitabine-based chemotherapy is the standard treatment for pancreatic cancer. However, the issue of resistance remains unresolved. The aim of this study was to identify microRNAs (miRNAs) that govern the resistance to gemcitabine in pancreatic cancer.

Methods:

miRNA microarray analysis using gemcitabine-resistant clones of MiaPaCa2 (MiaPaCa2-RGs), PSN1 (PSN1-RGs), and their parental cells (MiaPaCa2-P, PSN1-P) was conducted. Changes in the anti-cancer effects of gemcitabine were studied after gain/loss-of-function analysis of the candidate miRNA. Further assessment of the putative target gene was performed in vitro and in 66 pancreatic cancer clinical samples.

Results:

miR-320c expression was significantly higher in MiaPaCa2-RGs and PSN1-RGs than in their parental cells. miR-320c induced resistance to gemcitabine in MiaPaCa2. Further experiments showed that miR-320c-related resistance to gemcitabine was mediated through SMARCC1, a core subunit of the switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex. In addition, clinical examination revealed that only SMARCC1-positive patients benefited from gemcitabine therapy with regard to survival after recurrence (P=0.0463).

Conclusion:

The results indicate that miR-320c regulates the resistance of pancreatic cancer cells to gemcitabine through SMARCC1, suggesting that miR-320c/SMARCC1 could be suitable for prediction of the clinical response and potential therapeutic target in pancreatic cancer patients on gemcitabine-based therapy.     

MicroRNA-195 suppresses tumor cell proliferation and metastasis by directly targeting BCOX1 in prostate carcinoma

Elucidation of the downstream targets regulated by the metastasis-suppressive miRNAs can shed light on the metastatic processes in prostate cancer (PCa). We conducted microarray analyses and found that miR-195 was significantly decreased in metastatic PCa. Low miR-195 expression is an independent prognostic factor for poor biochemical recurrence-free and overall survival. Forced expression of miR-195 in PCa cells drastically inhibits proliferation, migration and invasion in vitro and inhibits tumor growth and metastasis in vivo. BCOX1 is identified as a direct target of miR-195 in PCa, and is found to be drastically increased in metastatic PCa. BCOX1 knockdown phenotypically copies miR-195-induced phenotypes, whereas forced expression of BCOX1 reverses the effects of miR-195. Collectively, this is the first report unveils that loss of miR-195 expression and thus uncontrolled BCOX1 upregulation might drive PCa metastasis.

Electronic supplementary material

The online version of this article (doi:10.1186/s13046-015-0209-7) contains supplementary material, which is available to authorized users.     

MicroRNA-146a constrains multiple parameters of intestinal immunity and increases susceptibility to DSS colitis

Host-microbial interactions within the mammalian intestines must be properly regulated in order to promote host health and limit disease. Because the microbiota provide constant immunological signals to intestinal tissues, a variety of regulatory mechanisms have evolved to ensure proper immune responses to maintain homeostasis. However, many of the genes that comprise these regulatory pathways, including immune-modulating microRNAs (miRNAs), have not yet been identified or studied in the context of intestinal homeostasis. Here, we investigated the role of microRNA-146a (miR-146a) in regulating intestinal immunity and barrier function and found that this miRNA is expressed in a variety of gut tissues in adult mice. By comparing intestinal gene expression in WT and miR-146a−/− mice, we demonstrate that miR-146a represses a subset of gut barrier and inflammatory genes all within a network of immune-related signaling pathways. We also found that miR-146a restricts the expansion of intestinal T cell populations, including Th17, Tregs, and Tfh cells. GC B cells, Tfh ICOS expression, and the production of luminal IgA were also reduced by miR-146a in the gut. Consistent with an enhanced intestinal barrier, we found that miR-146a−/− mice are resistant to DSS-induced colitis, a model of Ulcerative Colitis (UC), and this correlated with elevated colonic miR-146a expression in human UC patients. Taken together, our data describe a role for miR-146a in constraining intestinal barrier function, a process that alters gut homeostasis and enhances at least some forms of intestinal disease in mice.