MicroRNAs: novel factors in clinical diagnosis and prognosis for nasopharyngeal carcinoma

MicroRNAs: novel factors in clinical diagnosis and prognosis for nasopharyngeal carcinoma
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MicroRNA:鼻咽癌临床诊断和预后的新因素

DOI:
10.1038/aps.2012.98
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发表时间:
2012-07
影响因子:
8.2
通讯作者:
Li, Yao
Li, Yao
中科院分区:
医学1区
文献类型:
--
作者:
Yang, Shu;Li, Yao

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鼻咽癌(NPC)是一种非淋巴瘤性、鳞状细胞恶性肿瘤,起源于鼻咽上皮细胞衬里。组织学上,NPC分为3种类型:角化性鳞状细胞癌(WHO I型)、分化的非角化性鳞状细胞癌(WHO II型)和未分化癌(WHO III型)。与其他上消化道恶性肿瘤相比,鼻咽癌在流行病学、病理学和临床表现上是一种特殊类型的头颈部肿瘤。NPC的病因涉及多种因素,包括遗传易感性、化学致癌物暴露和EB病毒(EBV)感染[1]。在一些地区,特别是中国南部和东南亚部分地区,这种癌症以地方病形式发生,发病率比其他地区高10至30倍,组织学上通常属于WHO II型和III型。而在西方,NPC是散发性的,通常属于WHO I型。在北方非洲和阿拉斯加的因纽特人中发病率也有所增加[2,3]。MicroRNA(miRNAs)是一类长度为19-25个核苷酸的小的非编码RNA分子,其通过结合靶向转录物的3 '-非翻译区(3'-UTR)负调控基因表达,导致mRNA切割或翻译抑制[4]。大约30%的人类基因由miRNAs调控。MicroRNA在许多类型的癌症中经常被失调,并且在肿瘤发生中起关键作用,其调节癌基因或肿瘤抑制基因的表达。在最近一期的Lancet Oncol杂志中,Liu等[5]报道了41种miRNA在鼻咽癌和非癌鼻咽炎组织中差异表达(倍数变化≥ 2.5,假发现率0)。先前的报道表明,与正常上皮组织相比,miRNA在鼻咽癌中异常表达,并通过改变其mRNA靶点的表达促进侵袭性肿瘤表型[6-8]。例如,Sengupta等人[6]使用miRNA微阵列研究了31个NPC和10个正常组织中207个miRNA的表达,并证明了miR-29 c通过调节编码细胞外基质蛋白的mRNA参与NPC转移。Chen等[7]采用stemloop实时荧光定量PCR方法研究了270种人类miRNAs在13例鼻咽癌组织和9例癌旁正常组织中的表达情况,发现35种miRNAs在鼻咽癌组织中的表达发生了显著变化,从而推断某些癌症相关通路中富含下调的miRNAs靶点。我们还用微阵列证明了34种miRNAs在8种NPC和4种正常组织中差异表达[8]。此外,我们确定了2个新的途径,改变的miRNA的目标,与NPC的发展密切相关,并推断在NPC中以c-Myc为中心的miRNA调控网络。这些研究结果表明,一些重要的miRNAs可作为鉴别诊断鼻咽癌和非癌性鼻咽炎患者的标志物。有趣的是,在所有4项研究中,miR-34 c在NPC标本中均被发现低表达,这表明该miRNA在NPC的发生和进展中起着至关重要的作用。然而,miR-34 c在鼻咽癌中的作用尚不清楚。另外,4篇文献中有3篇报道3种miRNA(miR-34 b、miR-29 c和miR-100)在NPC中表达下调。在此,我们关注miR-29家族,因为miR-29 a和miR-29 b在NPC中也低表达,如4份报告中的2份所示。我们认为miR-29...
Nasopharyngeal carcinoma (NPC) is a non-lymphomatous, squamous cell malignancy arising from the epithelial cells lining of the nasopharynx. Histologically, NPC has been classified into 3 types: keratinizing squamous cell carcinoma (WHO type I), differentiated non-keratinizing squamous cell carcinoma (WHO type II) and undifferentiated carcinomas (WHO type III). Compared to other malignant tumours of the upper aero digestive tract, NPC is a special type of head and neck cancer in terms of epidemiology, pathology and clinical presentation. The etiology of NPC involves multiple factors, including genetic susceptibility, exposure to chemical carcinogens and Epstein-Barr virus (EBV) infection [1]. In some regions, notably the southern parts of China, and parts of Southeast Asia, this cancer occurs in an endemic form with an incidence 10-to 30-fold higher than in the other regions and, histologically, usually belongs to WHO type II and III. In the west, however, NPC occurs sporadically and usually belongs to WHO type I. There is also increased incidence in northern Africa and the Inuit of Alaska [2, 3]. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules, 19–25 nucleotides in length, that negatively regulate gene expression through binding the 3’-untranslated region (3’-UTR) of targeted transcripts, resulting in mRNA cleavage or translation repression [4]. About 30% of human genes are regulated by miRNAs. MicroRNAs are frequently deregulated in many types of cancers, and play critical roles in tumorigenesis, which regulate the expression of oncogenes or tumour suppressor genes. In a recent issue of Lancet Oncol, Liu et al [5] reported that 41 miRNAs were differentially expressed between nasopharyngeal carcinoma and noncancer nasopharyngitis tissues (fold change≥ 2.5, false discovery rate 0). Previous reports showed that miRNAs were aberrantly expressed in nasopharyngeal carcinoma compared with normal epithelial tissue, and promoted an aggressive tumour phenotype by changing the expression of their mRNA targets [6–8]. For instance, Sengupta et al [6] investigated the expressions of 207 miRNAs in 31 NPCs and 10 normal tissues with miRNA microarrays, and demonstrated the involvement of miR-29c in NPC metastasis by regulating mRNAs encoding extracellular matrix proteins. Chen et al [7] studied the expression of 270 human miRNAs in 13 NPC samples in comparison with 9 adjacent normal tissues using a stemloop real-time PCR assay, and found the expressions of 35 miRNAs were significantly altered in NPC, thus inferred that some cancer-related pathways enriched with targets of down-regulated miRNAs. We also demonstrated with microarray that 34 miRNAs were differentially expressed between 8 NPC and 4 normal tissues [8]. Furthermore, we identified 2 novel pathways, targeted by the altered miRNAs, were strongly associated with NPC development, and a c-Myc centred miRNA regulatory network was inferred in NPC. These reports indicate that some important miRNAs can be used as markers for differential diagnosis of NPC from non-cancer nasopharyngitis patients. Interestingly, in all the 4 studies, miR-34c has been found underexpression in NPC specimens, suggesting that that this miRNA plays a crucial role in NPC development and progression. However, the functions of miR-34c were still unclear in NPC. Additionally, 3 out of the 4 reports showed that 3 miRNAs (miR-34b, miR-29c and miR-100) in NPC were downregulated. Here, we pay attention to the miR-29 family because miR-29a and miR-29b were also under-expressed in NPC as shown in 2 of the 4 reports. We consider that the miR-29 …
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