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首页> 外文期刊>Epigenetics & Chromatin >Aberrant methylation-mediated downregulation of lncRNA SSTR5-AS1 promotes progression and metastasis of laryngeal squamous cell carcinoma
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Aberrant methylation-mediated downregulation of lncRNA SSTR5-AS1 promotes progression and metastasis of laryngeal squamous cell carcinoma

机译：异常甲基化介导的lncRNA SSTR5-AS1下调促进喉鳞状细胞癌的进展和转移

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Laryngeal squamous cell carcinoma (LSCC) is among the most common malignant tumors with poor prognosis. Accumulating evidences have identified the important roles of long noncoding RNAs (lncRNAs) in the initiation and progression of various cancer types; however, the global lncRNAs expression profile for metastatic LSCC is limited. In the present study, we screen expression profiles of lncRNAs in advanced LSCC patients with paired tumor tissues and corresponding normal tissues by microarrays. We identify numerous differentially expressed transcripts, and after the necessary verification of the transcripts expression in expanded samples, we experimentally validate the expression patterns of the remarkable low expressed gene, SSTR5, and its antisense lncRNA, SSTR5-AS1. Downregulation of SSTR5 is detected in LSCC tissues and laryngeal carcinoma cells. Aberrant DNA hypermethylation of the CpG sites clustered in the exon 1 and accumulation of inactive histone modifications at SSTR5 promoter region may be epigenetic mechanisms for its inactivation in LSCC. SSTR5-AS1 may play antitumor role in LSCC and may be regulated by the hypermethylation of the same CpG sites with SSTR5. SSTR5-AS1 inhibits laryngeal carcinoma cells proliferation, migration, and invasion. SSTR5-AS1 increases the enrichment of MLL3 and H3K4me3 at the promoter region of SSTR5 by interacting with MLL3 and further induces the transcription of SSTR5. Furthermore, SSTR5-AS1 interacts with and recruits TET1 to its target gene E-cadherin to activate its expression. These findings suggest that the identified lncRNAs and mRNAs may be potential biomarkers in metastatic LSCC, and SSTR5-AS1 may act as a tumor suppressor as well as a potential biomarker for antitumor therapy.
机译：喉鳞状细胞癌（LSCC）是最常见的预后不良的恶性肿瘤。越来越多的证据确定了长非编码RNA（lncRNA）在各种癌症类型的发生和发展中的重要作用。然而，转移性LSCC的全球lncRNAs表达谱是有限的。在本研究中，我们通过微阵列筛选了具有配对肿瘤组织和相应正常组织的晚期LSCC患者中lncRNA的表达谱。我们鉴定出许多差异表达的转录本，并在扩大样本中对转录本表达进行必要的验证后，我们通过实验验证了显着的低表达基因SSTR5及其反义lncRNA SSTR5-AS1的表达模式。在LSCC组织和喉癌细胞中检测到SSTR5的下调。聚集在外显子1上的CpG位点的异常DNA超甲基化和SSTR5启动子区域失活的组蛋白修饰的积累可能是其在LSCC中失活的表观遗传机制。 SSTR5-AS1可能在LSCC中发挥抗肿瘤作用，并可能受SSTR5相同CpG位点的甲基化作用所调节。 SSTR5-AS1抑制喉癌细胞的增殖，迁移和侵袭。 SSTR5-AS1通过与MLL3相互作用增加SSTR5启动子区域MLL3和H3K4me3的富集，并进一步诱导SSTR5的转录。此外，SSTR5-AS1与TET1相互作用并招募其目标基因E-钙粘着蛋白以激活其表达。这些发现表明，所鉴定的lncRNA和mRNA可能是转移性LSCC中的潜在生物标志物，而SSTR5-AS1可能充当肿瘤抑制因子以及抗肿瘤治疗的潜在生物标志物。

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