Aberrant chimeric RNA GOLM1-MAK10 encoding a secreted fusion protein as a molecular signature for human esophageal squamous cell carcinoma.
Aberrant chimeric RNA GOLM1-MAK10 encoding a secreted fusion protein as a molecular signature for human esophageal squamous cell carcinoma.
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编码分泌融合蛋白的异常嵌合 RNA GOLM1-MAK10 作为人食管鳞状细胞癌的分子特征
DOI：
10.18632/oncotarget.1465
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发表时间：
2013-11
期刊：
影响因子：
--
通讯作者：
Yen L
中科院分区：
文献类型：
--
作者：
Zhang H;Lin W;Kannan K;Luo L;Li J;Chao PW;Wang Y;Chen YP;Gu J;Yen L
越来越多的人认识到，嵌合RNA可以发挥一种新的细胞复杂性，有助于肿瘤发生和癌症进展，并可用作分子生物标志物和治疗靶点。迄今为止，尚未在食管癌中鉴定出融合嵌合RNA，食管癌是世界上第六大最常见的癌症死亡原因。在分析来自患者和癌细胞系的食管鳞状细胞癌（ESCC）中的32种复发性癌症嵌合RNA的表达时，我们鉴定了GOLM 1-MAK 10作为ESCC中高度癌症富集的嵌合RNA。原位杂交显示，嵌合体的表达主要限于患者肿瘤中的癌细胞，并且在正常受试者的非肿瘤性食管组织中几乎检测不到。异常嵌合体与组织分化程度和淋巴结转移密切相关。此外，我们证明嵌合体GOLM 1-MAK 10编码分泌的融合蛋白。机制研究表明，GOLM 1-MAK 10可能来源于转录通读/剪接，而不是由融合基因产生。总的来说，这些发现为ESCC的分子机制提供了新的见解，并为未来的治疗提供了新的潜在靶点。从GOLM 1-MAK 10翻译的分泌的融合蛋白也可以用作通过标准非侵入性测定可检测的独特蛋白质特征。这些观察结果是至关重要的，因为没有临床上有用的分子特征可用于检测这种致命疾病或监测治疗反应。
It is increasingly recognized that chimeric RNAs may exert a novel layer of cellular complexity that contributes to oncogenesis and cancer progression, and could be utilized as molecular biomarkers and therapeutic targets. To date yet no fusion chimeric RNAs have been identified in esophageal cancer, the 6th most frequent cause of cancer death in the world. While analyzing the expression of 32 recurrent cancer chimeric RNAs in esophageal squamous cell carcinoma (ESCC) from patients and cancer cell lines, we identified GOLM1-MAK10, as a highly cancer-enriched chimeric RNA in ESCC. In situ hybridization revealed that the expression of the chimera is largely restricted to cancer cells in patient tumors, and nearly undetectable in non-neoplastic esophageal tissue from normal subjects. The aberrant chimera closely correlated with histologic differentiation and lymph node metastasis. Furthermore, we demonstrate that chimera GOLM1-MAK10 encodes a secreted fusion protein. Mechanistic studies reveal that GOLM1-MAK10 is likely derived from transcription read-through/splicing rather than being generated from a fusion gene. Collectively, these findings provide novel insights into the molecular mechanism involved in ESCC and provide a novel potential target for future therapies. The secreted fusion protein translated from GOLM1-MAK10 could also serve as a unique protein signature detectable by standard non-invasive assays. These observations are critical as there is no clinically useful molecular signature available for detecting this deadly disease or monitoring the treatment response.
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影响因子：
158.5
作者：
Druker, Brian J.;Guilhot, Francois;Larson, Richard A.
通讯作者：
Larson, Richard A.
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
影响因子：
56.9
作者：
Tomlins, SA;Rhodes, DR;Chinnaiyan, AM
通讯作者：
Chinnaiyan, AM
影响因子：
10.5
作者：
Zhang, Hao;Singh, Rajesh R.;Kumar, Rakesh
通讯作者：
Kumar, Rakesh
嵌合体形成：由嵌合RNA转录物编码的蛋白质的潜在功能。
影响因子：
7
作者：
Frenkel-Morgenstern M;Lacroix V;Ezkurdia I;Levin Y;Gabashvili A;Prilusky J;Del Pozo A;Tress M;Johnson R;Guigo R;Valencia A
通讯作者：
Valencia A