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Expression of TMEM207 in Colorectal Cancer: Relation between TMEM207 and Intelectin-1

机译:TMEM207在大肠癌中的表达:TMEM207与Intelectin-1的关系。

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摘要

Recent research advances highlighted an intestinal goblet cell-produced lectin, intelectin-1 (also known as omentin-1), as a tumor suppressor. One study indicated that downregulation of intelectin-1 may be related to the unfavorable prognosis among patients with colorectal carcinoma at an advanced stage. The present study was aimed at analyzing the expression of a hitherto uncharacterized transmembrane protein TMEM207 in colorectal carcinoma, and we found that the TMEM207 function is linked to intelectin-1 processing. With specific antibodies, TMEM207 immunoreactivity was detected in 38 of 216 colorectal cancer tissue samples. TMEM207 immunoreactivity correlated inversely with lymph node metastatic status (p < 0.01). TMEM207 expression significantly correlated with the mucinous phenotype of colorectal carcinoma. A coimmunoprecipitation assay revealed an interaction between intelectin-1 and TMEM207 in colorectal cancer cells. A proximal ligation assay indicated that intelectin-1 and TMEM207 were colocalized to the cytoplasm of the colorectal cancer cells. A small-interfering-RNA-mediated knockdown of TMEM207 increased polyubiquitination and proteasome degradation of intelectin-1 in cultured colorectal cancer cells and decreased intelectin-1 secretion. These findings indicate that a loss of TMEM207 expression leads to insufficient intelectin-1 production thus promoting colorectal carcinogenesis.
机译:最近的研究进展突出了肠道杯状细胞产生的凝集素intelectin-1(也称为omentin-1),它是一种肿瘤抑制因子。一项研究表明,intelectin-1的下调可能与晚期大肠癌患者的不良预后有关。本研究旨在分析迄今未表征的跨膜蛋白TMEM207在大肠癌中的表达,我们发现TMEM207的功能与intelectin-1的加工有关。使用特异性抗体,在216个大肠癌组织样本中的38个中检测到TMEM207免疫反应性。 TMEM207免疫反应性与淋巴结转移状态呈负相关(p <0.01)。 TMEM207的表达与大肠癌的黏液表型显着相关。一项免疫沉淀试验表明,大肠癌细胞中intelectin-1和TMEM207之间存在相互作用。近端连接试验表明,intelectin-1和TMEM207共定位于大肠癌细胞的细胞质。 TMEM207的小干扰RNA介导的敲低增加了培养的结直肠癌细胞中intelectin-1的多泛素化和蛋白酶体降解,并减少了intelectin-1的分泌。这些发现表明,TMEM207表达的丧失导致intelectin-1的产生不足,从而促进了结直肠癌的发生。

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