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长链非编码 RNA TCONS_00068220 通过调节上皮-间充质转化标志物 E-钙黏蛋白促进乳腺癌进展。

Long Noncoding RNA TCONS_00068220 Promotes Breast Cancer Progression by Regulating Epithelial-Mesenchymal Transition Marker E-Cadherin.

机构信息

Department of Breast and Thyroid Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China (mainland).

Department of Breast and Thyroid Surgery, Hospital of Chinese Medicine of Taian City, Taian, Shandong, China (mainland).

出版信息

Med Sci Monit. 2021 Mar 15;27:e929832. doi: 10.12659/MSM.929832.

Abstract

BACKGROUND Long noncoding RNAs (lncRNAs) play essential roles in the regulation of breast cancer development. We herein investigated the potential role of lncRNA TCONS_00068220 in breast cancer pathogenesis. MATERIAL AND METHODS The expression levels of TCONS_00068220 in breast cancer tissues were measured by qRT-PCR. Afterwards, TCONS_00068220 was (1) overexpressed in MCF-7 breast cancer cells, and (2) silenced in MDA-MB-231 cells. Then, CCK-8 and transwell assays were conducted to detect the impact of TCONS_00068220 on cell proliferation, migration, and invasion. The expression of the epithelial-mesenchymal transition (EMT) marker E-cadherin was detected by western blot assay after upregulation or downregulation of TCONS_00068220. RESULTS TCONS_00068220 was remarkably upregulated in breast cancer tissues compared with non-cancerous tissues. In addition, TCONS_00068220 level was significantly correlated with lymphatic metastasis, Ki67 index, clinical stage, and differentiation grade. All breast cancer cell lines displayed a higher expression level of TCONS_00068220 compared with the normal breast epithelial cell line MCF-10A. Furthermore, enhanced expression of TCONS_00068220 in MCF-7 cells promoted cell proliferation, migration, invasion, and EMT, whereas TCONS_00068220 knockdown in MDA-MB-231 cells led to the opposite results. E-cadherin was negatively regulated by TCONS_00068220 in both breast cancer tissues and cell lines. Finally, TCONS_00068220 regulated MCF-7 and MDA-MB-231 cell behaviors by downregulating E-cadherin. CONCLUSIONS TCONS_00068220 promotes breast cancer cell proliferation, migration, and invasion, while facilitating the process of EMT by interacting with E-cadherin and suppressing its expression. Therefore, it may potentially serve as an oncogene in breast cancer progression.

摘要

背景

长链非编码 RNA(lncRNA)在乳腺癌的发展中起着至关重要的调节作用。本研究旨在探讨 lncRNA TCONS_00068220 在乳腺癌发病机制中的潜在作用。

材料与方法

采用 qRT-PCR 检测乳腺癌组织中 TCONS_00068220 的表达水平。然后,在 MCF-7 乳腺癌细胞中转染 TCONS_00068220 过表达载体,在 MDA-MB-231 细胞中转染 TCONS_00068220 沉默载体。采用 CCK-8 法和 Transwell 实验检测 TCONS_00068220 对细胞增殖、迁移和侵袭的影响。通过上调或下调 TCONS_00068220 表达水平,采用 Western blot 检测上皮-间充质转化(EMT)标志物 E-钙黏蛋白的表达。

结果

与非癌组织相比,乳腺癌组织中 TCONS_00068220 表达明显上调。此外,TCONS_00068220 水平与淋巴转移、Ki67 指数、临床分期和分化程度显著相关。与正常乳腺上皮细胞系 MCF-10A 相比,所有乳腺癌细胞系均显示出更高的 TCONS_00068220 表达水平。此外,MCF-7 细胞中 TCONS_00068220 的表达增强促进了细胞增殖、迁移、侵袭和 EMT,而 MDA-MB-231 细胞中 TCONS_00068220 的敲低则导致相反的结果。在乳腺癌组织和细胞系中,E-钙黏蛋白受 TCONS_00068220 的负调控。最后,TCONS_00068220 通过下调 E-钙黏蛋白调节 MCF-7 和 MDA-MB-231 细胞的行为。

结论

TCONS_00068220 通过与 E-钙黏蛋白相互作用并抑制其表达,促进乳腺癌细胞的增殖、迁移和侵袭,同时促进 EMT 过程。因此,它可能是乳腺癌进展中的潜在癌基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f083/7976663/31d7b029d941/medscimonit-27-e929832-g001.jpg

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