口腔黏膜恶性黑色素瘤转移淋巴结中长链非编码 RNA 表达谱的全基因组分析。

A comprehensive genome-wide analysis of the long noncoding RNA expression profile in metastatic lymph nodes of oral mucosal melanoma.

机构信息

Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, China; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai, China.

出版信息

Gene. 2018 Oct 30;675:44-53. doi: 10.1016/j.gene.2018.06.064. Epub 2018 Jun 28.

DOI:10.1016/j.gene.2018.06.064

PMID:29960071

Abstract

BACKGROUND & AIM: Oral mucosal melanoma (OMM) is a kind of malignancy with extremely rare morbidity. It exhibits a poorer biological behavior and clinical outcome compared with cutaneous melanoma. lncRNAs are endogenous cellular RNA transcripts with no protein-coding potential and are associated with oncogenesis through cis- or trans-acting mechanisms. Despite increased evidence that proved lncRNAs have vital roles in tumorigenesis of mucosal melanoma, little is known about their functions in the progress of lymph node dissemination of OMM.

METHOD

Here, we constructed a lncRNA and mRNA microarray using six metastatic lymph nodes and paired-matched non-metastatic lymph nodes. Then, we performed RT-PCR to validate the microarray data both in primary and metastases. We further constructed lncRNA and mRNA co-expressing networks and analyzed the biological functions by Gene Ontology (GO) and pathway analyses for dysregulated lncRNAs and mRNAs. Cis- and trans-regulation analysis were also performed to explore the specific mechanism of lncRNAs in OMM.

RESULT

Our results showed that 570 lncRNAs were upregulated with 292 lncRNAs downregulated in the metastatic OMM tissues. The results of RT-PCR were consistent with our microarray dataset both in primary and metastases. Gene Ontology (GO) and pathway analyses indicated that they play an important role in the melanin biosynthetic process, new growing cell tip and lysosomes in metastatic OMM. In the cis-regulation analysis, we observed metastasis-associated gene, PLEKHA5, the cis gene of lnc-AEBP2-1_1 and lnc-AEBP2-2_1, and microphthalmia-associated transcription factor (MITF), the cis gene of SAMMSON_3, SAMMSON_5 and lnc-MITF-5_1. In the trans-regulation analysis, CTBP2 and SUZ12 regulated lncRNA expression in the core TF-lncRNA-gene network.

CONCLUSION

Our results suggest that lncRNAs may be involved in the metastasis of OMM, and further investigation is needed to focus on the biological functions and the underlining molecular mechanisms exerted by these dysregulated lncRNAs in OMM.

摘要

背景与目的

口腔黏膜黑色素瘤（OMM）是一种发病率极低的恶性肿瘤。与皮肤黑色素瘤相比，其生物学行为和临床预后较差。lncRNAs 是一种内源性细胞 RNA 转录物，没有蛋白编码潜能，并通过顺式或反式作用机制与肿瘤发生相关。尽管越来越多的证据证明 lncRNAs 在黏膜黑色素瘤的发生中具有重要作用，但它们在 OMM 淋巴结转移进展中的功能知之甚少。

方法

在这里，我们使用六个转移性淋巴结和配对的非转移性淋巴结构建了 lncRNA 和 mRNA 微阵列。然后，我们进行 RT-PCR 验证以验证原发性和转移性微阵列数据。我们进一步构建了 lncRNA 和 mRNA 共表达网络，并通过基因本体论（GO）和通路分析对失调的 lncRNAs 和 mRNAs 进行了生物功能分析。还进行了顺式和反式调控分析，以探索 lncRNAs 在 OMM 中的特定机制。

结果

我们的结果表明，在转移性 OMM 组织中，有 570 个 lncRNAs 上调，292 个 lncRNAs 下调。RT-PCR 的结果与我们的微阵列数据集在原发性和转移性组织中均一致。GO 和通路分析表明，它们在转移性 OMM 的黑色素生物合成过程、新生长细胞尖端和溶酶体中发挥重要作用。在顺式调控分析中，我们观察到转移相关基因 PLEKHA5、lnc-AEBP2-1_1 和 lnc-AEBP2-2_1 的顺式基因、小眼畸形相关转录因子（MITF）、SAMMSON_3、SAMMSON_5 和 lnc-MITF-5_1 的顺式基因。在反式调控分析中，CTBP2 和 SUZ12 调节核心 TF-lncRNA-基因网络中的 lncRNA 表达。