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MPZL1 在晚期胆囊癌中高表达,并促进人胆囊癌细胞 GBC-SD 的侵袭行为。

MPZL1 is highly expressed in advanced gallbladder carcinoma and promotes the aggressive behavior of human gallbladder carcinoma GBC‑SD cells.

机构信息

Department of Hepato‑Pancreato‑Biliary Surgical Oncology, Chinese PLA General Hospital, Beijing 100853, P.R. China.

Department of General Surgery, China‑Japan Friendship Hospital, Beijing 100029, P.R. China.

出版信息

Mol Med Rep. 2019 Sep;20(3):2725-2733. doi: 10.3892/mmr.2019.10506. Epub 2019 Jul 18.

Abstract

Myelin protein 0‑like 1 (MPZL1) has been reported to have a role in hepatocellular carcinoma. However, to the best of our knowledge, there have been no studies on the function and molecular mechanism of MPZL1 gene in gallbladder carcinoma. The present study confirmed that MPZL1 was upregulated in four gallbladder carcinoma tissues according to the mRNA microarray analysis. The results of the immunohistochemical analysis of tissues from 82 patients with gallbladder carcinoma demonstrated that patients with advanced tumor stages (both T and N stage) had higher positive expression of MPZL1. Moreover, a total of 20 cases of gallbladder carcinoma and matched paired paracarcinoma tissues along with 20 samples of healthy gallbladder tissue from patients with cholecystitis were analyzed using reverse transcription‑quantitative PCR and western blotting. The results demonstrated that the expression of MPZL1 in gallbladder carcinoma tissues was significantly higher than that of paired paracarcinoma tissues and randomly matched normal gallbladder epithelial tissues. According to the Tumor‑Node‑Metastasis classification, the expression level of MPZL1 protein in stage IV gallbladder carcinoma was significantly higher than that in stage III gallbladder carcinoma. The enhanced expression of MPZL1 gene appeared to improve the migration ability of GBC‑SD cells. Conversely, GBC‑SD cells that transfected with MPZL1 siRNA exhibited decreased migration ability. The results of proliferation experiments showed that the knockdown of MPZL1 siRNA caused impairments in GBC‑SD cell proliferation. On the contrary, the overexpression of MPZL1 increased the proliferation ability of GBC‑SD cells. The results of flow cytometry analyses indicated that the upregulation of MPZL1 had an anti‑apoptotic effect on GBC‑SD cells. In conclusion, the present study showed that the expression and protein levels of MPZL1 were significantly higher in gallbladder carcinoma tissues, especially in patients diagnosed with advanced tumor stages. Overexpression of MPZL1 may have promoted the invasion, metastasis, proliferation and survival of GBC‑SD cells.

摘要

髓鞘蛋白 0 样 1 (MPZL1) 已被报道在肝细胞癌中具有作用。然而,据我们所知,尚未有研究报道 MPZL1 基因在胆囊癌中的功能和分子机制。本研究通过 mRNA 微阵列分析证实,MPZL1 在 4 例胆囊癌组织中上调。对 82 例胆囊癌患者组织的免疫组织化学分析结果表明,肿瘤进展期(T 期和 N 期均)患者的 MPZL1 阳性表达较高。此外,采用逆转录-定量 PCR 和 Western blot 分析了 20 例胆囊癌及配对癌旁组织和 20 例来自胆囊炎患者的正常胆囊组织。结果表明,胆囊癌组织中 MPZL1 的表达明显高于配对癌旁组织和随机匹配的正常胆囊上皮组织。根据肿瘤-淋巴结-转移分期,IV 期胆囊癌组织中 MPZL1 蛋白的表达水平明显高于 III 期胆囊癌。MPZL1 基因的增强表达似乎提高了 GBC-SD 细胞的迁移能力。相反,转染 MPZL1 siRNA 的 GBC-SD 细胞迁移能力降低。增殖实验结果表明,MPZL1 siRNA 的敲低导致 GBC-SD 细胞增殖受损。相反,MPZL1 的过表达增加了 GBC-SD 细胞的增殖能力。流式细胞术分析结果表明,MPZL1 的上调对 GBC-SD 细胞具有抗凋亡作用。综上所述,本研究表明,MPZL1 的表达和蛋白水平在胆囊癌组织中明显升高,尤其是在诊断为肿瘤进展期的患者中。MPZL1 的过表达可能促进了 GBC-SD 细胞的侵袭、转移、增殖和存活。

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