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UBE2S 调控 Wnt/β-连环蛋白信号通路并促进非小细胞肺癌的进展。

Ube2S regulates Wnt/β-catenin signaling and promotes the progression of non-small cell lung cancer.

机构信息

Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, 110001, Shenyang, China.

出版信息

Int J Med Sci. 2020 Jan 14;17(2):274-279. doi: 10.7150/ijms.40243. eCollection 2020.

DOI:10.7150/ijms.40243
PMID:32038111
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6990889/
Abstract

Ubiquitin conjugating enzyme E2S (Ube2S) plays important roles in cancer development in some malignant tumors. However, the functions and related molecular network of Ube2S in non-small cell lung cancer are not fully understood. In the current study, we examined the expression of Ube2S in non-small cell lung cancer and its clinicopathological significance. We also investigated the molecules and pathways regulated by Ube2S. An immunostaining study showed that the positive rate of Ube2s expression in lung cancer tissues was higher than that in normal lung tissues ( < 0.05). Upregulated Ube2S expression in cancer tissues significantly correlated with clinical progression (TNM III versus I + II), lymph node metastasis, and shorter survival time of the patients ( < 0.05). When Ube2S was overexpressed in A549 cells, the abilities of these cells to proliferate and migrate were increased ( < 0.05). Moreover, Ube2S significantly upregulated the expression of β-catenin, cyclin D1, and MMP7 (novel molecules of the Wnt/β-catenin pathway), and the activity of this pathway ( < 0.05). In addition, a Wnt/β-catenin signaling inhibitor effectively abolished the function of Ube2S. These results indicate that Ube2S may be a novel marker contributing to lung cancer development, possibly through regulating canonical Wnt signaling.

摘要

泛素结合酶 E2S(Ube2S)在一些恶性肿瘤的癌症发展中发挥重要作用。然而,Ube2S 在非小细胞肺癌中的功能和相关分子网络尚未完全了解。在本研究中,我们研究了 Ube2S 在非小细胞肺癌中的表达及其临床病理意义。我们还研究了受 Ube2S 调控的分子和途径。免疫染色研究表明,肺癌组织中 Ube2s 表达的阳性率高于正常肺组织(<0.05)。癌症组织中上调的 Ube2S 表达与临床进展(TNM III 与 I+II)、淋巴结转移以及患者的生存时间缩短显著相关(<0.05)。当 A549 细胞中过表达 Ube2S 时,这些细胞的增殖和迁移能力增强(<0.05)。此外,Ube2S 显著上调了β-连环蛋白、细胞周期蛋白 D1 和 MMP7(Wnt/β-连环蛋白途径的新分子)的表达以及该途径的活性(<0.05)。此外,Wnt/β-连环蛋白信号抑制剂可有效消除 Ube2S 的功能。这些结果表明,Ube2S 可能是促进肺癌发展的新标志物,可能通过调节经典的 Wnt 信号。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9639/6990889/593a80d37159/ijmsv17p0274g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9639/6990889/7d0959b5403d/ijmsv17p0274g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9639/6990889/176a3fbddfed/ijmsv17p0274g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9639/6990889/78648790058f/ijmsv17p0274g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9639/6990889/d45404d63cb2/ijmsv17p0274g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9639/6990889/593a80d37159/ijmsv17p0274g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9639/6990889/7d0959b5403d/ijmsv17p0274g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9639/6990889/176a3fbddfed/ijmsv17p0274g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9639/6990889/78648790058f/ijmsv17p0274g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9639/6990889/d45404d63cb2/ijmsv17p0274g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9639/6990889/593a80d37159/ijmsv17p0274g005.jpg

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