Ji Fu-Jian, Wu Yuan-Yu, An Zhe, Liu Xue-Song, Jiang Jun-Nan, Chen Fang-Fang, Fang Xue-Dong
Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, China.
Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun, 130033, China.
Sci Rep. 2017 Nov 14;7(1):15488. doi: 10.1038/s41598-017-15448-9.
The expression of legumain which has been shown overexpressed in patients with metastatic gastric cancer is positively correlated to both disease progression and outcome, and negatively correlated to microRNA (miR)-3978 expression. The RNA-binding protein, poly r(C) binding protein 1 (PCBP1) was the most downregulated protein in the metastatic tissue specimens. Quantitative real-time PCR showed that PCBP1 expression is transcriptionally downregulated in peritoneal metastasis tissues. RNA immunoprecipitation experiments showed that PCBP1 and miR-3978 are sequestered in normal peritoneal tissue, but the complex is disrupted following metastatic progression. PCBP1 expression mimicked miR-3978 expression across gastric cancer patients. Finally, replenishment of PCBP1 or miR-3978 expression in the peritoneal metastasis cell line MKN45 decreased legumain protein expression and chemosensitized the cells to treatment with docetaxel. However, replenishment of one and concomitant depletion of the other failed to induce chemosensitivity to docetaxel. Replenishment of miR-3978 also resulted in induction of PCBP1 protein expression, potentially indicating that miR-3978 expression might downregulate a negative regulator targeting PCBP1. Our current study reveals PCBP1 as an additional biomarker in peritoneal metastasis. PCBP1 and miR-3978 expression were correlated and suggests a potential interplay of differential miRNA biogenesis and RNA binding protein during metastatic progression.
在转移性胃癌患者中已显示过表达的天冬酰胺酶表达与疾病进展和预后均呈正相关，与微小RNA（miR）-3978表达呈负相关。RNA结合蛋白多聚r（C）结合蛋白1（PCBP1）是转移性组织标本中下调最明显的蛋白。定量实时PCR显示，PCBP1表达在腹膜转移组织中受到转录下调。RNA免疫沉淀实验表明，PCBP1和miR-3978在正常腹膜组织中被隔离，但随着转移进展，该复合物被破坏。在胃癌患者中，PCBP1表达与miR-3978表达相似。最后，在腹膜转移细胞系MKN45中补充PCBP1或miR-3978表达可降低天冬酰胺酶蛋白表达，并使细胞对多西他赛治疗产生化学敏感性。然而，单独补充一种并同时耗尽另一种未能诱导对多西他赛的化学敏感性。补充miR-3978还导致PCBP1蛋白表达的诱导，这可能表明miR-3978表达可能下调靶向PCBP1的负调节因子。我们目前的研究揭示PCBP1是腹膜转移中的另一种生物标志物。PCBP1和miR-3978表达相关，提示在转移进展过程中，差异微小RNA生物合成和RNA结合蛋白可能存在潜在相互作用。
