微RNA-143在肿瘤研究中的新进展

微RNA-143(miR-143)在多种人类肿瘤中低表达,目前研究发现其参与了细胞发育、分化、增殖、凋亡等一系列重要生物学进程.miR-143可能的靶基因有细胞外信号调节激酶5(ERK5)、含3B的纤维连接蛋白Ⅲ型结构域(FNDC3B)、DNA甲基转移酶3A(DNMT3A)、K-ras等.miR-143通过对靶基因的调控参与肿瘤细胞的生长、侵袭、转移和耐药.miR-143与抗肿瘤药物联合应用将是肿瘤治疗的一个新方向.     

微小RNA-375在肿瘤中的表达及作用

微小RNA-375(miR-375)与多种肿瘤的发生发展密切相关,如肝癌、胃癌、胰腺癌、子宫内膜癌、食管癌、非小细胞肺癌等.miR-375相关的肿瘤发病机制主要包括其与特定靶基因结合,并在转录后水平降解mRNA或抑制蛋白翻译,发挥抑制细胞增殖、促进细胞凋亡、抑制侵袭转移等抑癌作用.miR-375有望成为肿瘤治疗的一个新靶点,并可能成为肿瘤诊断、治疗及预后判断的一个重要生物标志物.     

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.     

微RNA-126与肿瘤

微RNA(miRNA)-126通过靶向作用于表皮生长因子域7(EGFL7)、同源框A9(HOXA9)、胰岛素受体底物-1(IRS-1)、p85-β基因等,在转录后水平调控靶基因表达,在肿瘤形成中起重要作用.miRNA-126作为抑癌因子,在多种肿瘤中均下调,其抑癌作用及机制在肺癌、白血病、乳腺癌、宫颈癌等中均已得到证实.     

微RNA-126与肿瘤

微RNA（miRNA）-126通过靶向作用于表皮生长因子域7（EGFL7）、同源框A9（HOXA9）、胰岛素受体底物-1（IRS-1）、p85-β基因等,在转录后水平调控靶基因表达,在肿瘤形成中起重要作用.miRNA-126作为抑癌因子,在多种肿瘤中均下调,其抑癌作用及机制在肺癌、白血病、乳腺癌、宫颈癌等中均已得到证实.     

微小RNA-133在肿瘤中的表达及调控机制

微小RNA（miRNA）作为一种短链非编码RNA,是转录后调控网络中重要的调控因子。研究表明miR-133家族成员miR-133a和miR-133b能在基因转录后水平调控靶基因表皮生长因子受体、原癌基因等的表达,调控丝裂原活化蛋白激酶和蛋白激酶B等细胞信号通路,影响肿瘤细胞增殖、侵袭和迁移过程。miR-133在肿瘤形成与进展过程中发挥关键作用,可能成为肿瘤治疗的新靶点。     

微小RNA在乳腺癌耐药中的研究

乳腺癌的多药耐药(MDR)是造成乳腺癌治疗失败的关键因素.微小RNA (miRNA)是一种内源性表达小分子单链RNA,通过与靶基因的信使RNA结合调控基因的转录后表达.miRNA参与乳腺癌耐药形成的多种机制,是治疗耐药乳腺癌的可行靶点.寻找新的miRNA并研究其在乳腺癌耐药中的作用已成为当今研究的热点.     

微小RNA-451在乳腺癌细胞中的表达及其与耐药的关系

目的:研究人类微小RNA-451(Homo sapiens micro RNA-451,hsa-miR-451)在乳腺癌细胞中的表达及其与多柔比星(adriamycin,ADM)耐药的关系。方法:用实时荧光定量PCR一步法检测乳腺癌亲本细胞MCF-7和耐ADM细胞MCF-7/ADM中hsa-miR-451的表达;利用脂质体分别将成熟miR-451的模拟物(mimics)及阴性对照转染MCF-7/ADM细胞,然后采用实时荧光定量PCR法检测细胞中多药耐药基因1(multi-drug resistance gene 1,MDR1)mRNA的表达,蛋白质印迹法检测细胞中P-糖蛋白(P-glycoprotein,P-gp)的表达,MTT法检测不同浓度ADM作用下的细胞增殖情况。结果:miR-451在MCF-7/ADM耐药细胞中低表达,与亲本细胞MCF-7相比明显降低(P<0.05)。MCF-7/ADM细胞转染miR-451mimics后,MDR1 mRNA和P-gp蛋白的相对表达量比阴性对照转染组均明显下降(P<0.05);而miR-451 mimics转染组细胞对ADM的敏感性增加,其半数抑制浓度(half inhibition concentration,IC50)值与阴性对照转染组细胞相比差异有统计学意义(P<0.05)。结论:在乳腺癌耐药细胞MCF-7/ADM中miR-451异常低表达,可能通过作用于MDR1/P-gp参与乳腺癌细胞耐药的发生和发展。     

microRNA-1301-mediated inhibition of tumorigenesis

The relatively recent discovery of microRNAs has added a completely new dimension to the study of the regulation of tumor cells, but how they control cell behavior remains largely elusive. HepG2 cells were assigned to the miR-1301 group and the control group. RT-PCR, Western blotting, wound healing, the Transwell chamber migration and MTT assays, and apoptosis detection assays were used to analyze cell behavior of HepG2 cells after miR-1301 mimic transfection. Our study showed that miR-1301 was downregulated in HepG2 cells, and that miR-1301 inhibited migration and invasion of HepG2 cells and promoted cellular apoptosis after transfection with miR-1301 mimics. In addition, p53 mRNA and p53 protein expression was upregulated, and Bcl-2 and Bcl-xL mRNA and protein expression was downregulated in the miR-1301 group. These results indicate that miR-1301 may be an inhibitor of tumorigenesis in HepG2 cells.     

Methylation-mediated repression of microRNA-143 enhances MLL-AF4 oncogene expression

Fusion proteins containing the amino terminus of mixed lineage leukemia (MLL) are common in acute lymphoblastic leukemia (ALL) due to translocations. The MLL-AF4 fusion protein is generated by the translocation t(4;11)(q21;q23), and t(4;11)-positive ALL patients (MLL-AF4 ALL), have a notoriously poorer prognosis compared with patients with other MLL-associated leukemias. The detailed role of this fusion protein in leukemogenesis is not well understood. MicroRNAs (miRNAs) targeting the AF4 3' untranslated regions may modulate MLL-AF4 fusion protein levels, raising the question of whether regulation of these miRNAs are involved in the progression of MLL-AF4 ALL. In this study, we show that miR-143 was identified as a regulator of MLL-AF4 expression in MLL-AF4 ALL samples. Restoration of miR-143 in MLL-AF4-positive RS4;11 and MV4-11 cells induced apoptosis, negatively contributing to leukemia cell growth by reducing MLL-AF4 fusion protein levels. Furthermore, miR-143 was epigenetically repressed by promoter hypermethylation in MLL-AF4-positive primary blasts and cell lines, but not in normal bone marrow cells and MLL-AF4-negative primary blasts, which was directly associated with expression of the MLL-AF4 oncogene. This is the first study to show that miR-143 functions as a tumor suppressor in MLL-AF4 B-cell ALL. These data reveal the therapeutic promise of upregulating miR-143 expression for MLL-AF4 B-cell ALL.     

彩色多普勒超声联合血清微RNA-187、微RNA-143水平检测在胆囊癌早期诊断中的价值

目的:探讨彩色多普勒超声联合血清微RNA-187、微RNA-143水平检测在胆囊癌早期诊断中的价值。方法:选取2015年1月至2020年1月本院收治的90例胆囊癌患者（病例组）、90例胆囊良性病变患者（良性组）、90例正常人（健康组）,均行彩色多普勒超声检查,并采用实时定量PCR方法检测血清微RNA-187、微RNA-143表达水平,分析三者联合诊断胆囊癌的效能。结果:彩色多普勒超声检出胆囊癌57例（63.33%）,漏误诊33例（36.67%）;病例组随着临床分期升高血清微RNA-187表达增加,微RNA-143表达下降（P＜0.05）,病例组的血清微RNA-187表达高于良性组、健康组（P＜0.05）;良性组微RNA-187表达水平高于健康组（P＜0.05）;病例组的血清微RNA-143表达低于良性组、健康组（P＜0.05）;良性组微RNA-143表达水平低于健康组（P＜0.05）;超声和血清微RNA-187、微RNA-143联合诊断对直径≤10 mm的胆囊癌诊断符合率高于单独超声检查（P＜0.05）;ROC分析结果显示,彩色多普勒超声联合血清微RNA-187、微RNA-143诊断胆囊癌的曲线下面积（AUC）为0.946,灵敏度、特异度分别为90.00%、92.86%。结论:彩色多普勒超声能够显示胆囊壁、胆囊腔内的病变情况及胆囊与周围组织器官的关系,血清微RNA-187在胆囊癌患者中呈高表达,微RNA-143呈低表达,三者联合可进一步提高胆囊癌的早期诊断效能。     

Role of microRNA-143 in Fas-mediated apoptosis in human T-cell leukemia Jurkat cells

Treatment of Jurkat T cells with Fas-activating antibody (CH-11) facilitated rapid cell death that was shown to be caspase-dependent apoptosis. The expression of miR-143 was up-regulated during the apoptosis with time. The increased expression of miR-143 emerged from 1 to 2 h after the treatment, at which time the caspases-8 and -3 were also activated; and this increase was almost canceled by the pretreatment with an inhibitor of caspase-3 or -8. Furthermore, the transfection of Jurkat cells with mature miR-143 induced a significant growth suppression and enhancement of CH-11-induced apoptosis. On the contrary, an extracellular signal-regulated protein kinase 5 (ERK5), which was determined to be a target of miR-143 in colon cancer DLD-1 cells, was time-dependently down-regulated at the translational level after the treatment. During the apoptosis, the expression level of FasL was maintained and the level of nuclear-Foxo3a was increased in the early phase. These data suggest that the up-regulation of miR-143 could be related to the apoptosis in part by targeting ERK5, which leads to promotion of Foxo3a/FasL positive feedback loop.     

FHL蛋白家族在肿瘤发生发展中的作用研究进展

FHL家族是含有4个半LIM结构域的蛋白家族,现已在体内发现5个成员,即FHL1、FHL2、FHL3、FHL4和FHL5/ACT,不同成员的表达具有一定的组织特异性。FHL家族通过LIM结构域与其他蛋白相互作用,在转录调节、细胞增殖中发挥重要作用,与肺癌、胃癌、胰腺癌、卵巢癌、宫颈癌等多种肿瘤的发生发展密切相关。本文综述了FHL家族在多种肿瘤发生发展过程中的作用,提示FHL家族在肿瘤发生发展中存在广阔的研究空间,其在肿瘤生长调节中的作用和机理,对于FHL相关的肿瘤诊断、靶向治疗以及预后研究将有着重要意义,为肿瘤治疗提供了一个潜在靶点。     

MicroRNA-21在结直肠癌中的研究进展

结直肠癌是我国常见的消化系统恶性肿瘤之一。目前认为结直肠癌的形成是一个多因素、多步骤的过程,其具体的发病机制尚不清楚。microRNA（miRNA）是一类非编码的小分子RNA,能在转录后水平调控基因蛋白的表达,参与肿瘤细胞增殖、分化、侵袭和转移,对结直肠癌的发生和发展具有重要的作用。miRNA-21是当前研究miRNA在结直肠癌发病机制的热点之一,本文就miR-21在结直肠癌中的研究进展作一综述。      

The role of microRNA-196a in tumorigenesis,tumor progression,and prognosis

MicroRNAs are a large group of non-coding RNAs that have emerged as regulators of various biological processes, especially carcinogenesis and cancer progression. Recent evidence has shown that microRNA-196a (miR-196a) is upregulated in most types of tumors and involved in multiple biological processes via translational inhibition and mRNA cleavage, such as cell proliferation, migration, and invasion, mostly functioning as an oncogene. Dysregulation of miR-196a promotes oncogenesis and tumor progression. In this review, we summarize the upstream regulators, target genes, signaling pathways, and single nucleotide polymorphisms of miR-196a, which collectively affect cell proliferation, migration, and invasion. In addition, we review the clinical outcomes and significance of miR-196a. miR-196a may serve as a novel biomarker or target for diagnosis, prognosis, and therapy in several human cancers.