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上调的 lnc-肺癌相关转录本 1 增强了乳腺癌进展中的细胞迁移和侵袭。

Up-regulated lnc-lung cancer associated transcript 1 enhances cell migration and invasion in breast cancer progression.

机构信息

Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, China; Department of Breast Surgery, Yantai Yuhuangding Hospital, Yantai, China.

Department of Breast Surgery, Yantai Yuhuangding Hospital, Yantai, China.

出版信息

Biochem Biophys Res Commun. 2020 Jan 8;521(2):271-278. doi: 10.1016/j.bbrc.2019.08.040. Epub 2019 Oct 18.

Abstract

Breast cancer remains a leading cause of tumor-related deaths in the world. The pathogenesis contributing to breast cancer progression has not been fully understood. Increasing evidence suggests that long noncoding RNA (lncRNA) is implicated in various kinds of malignant cancers, including breast cancer. In the study, we attempted to explore the expression and effects of lnc-lung cancer associated transcript 1 (LUCAT1) on breast cancer development. Our results indicated that the expression of lnc-LUCAT1 was highly up-regulated in breast cancer tissues and cell lines. Over-expression of lnc-LUCAT1 enhanced cell proliferation, migration and invasion in breast cancer cell lines. Moreover, lnc-LUCAT1 was found to be a target of miR-7-5p. There was a negative correlation between lnc-LUCAT1 and miR-7-5p. The reduction of miR-7-5p was required in the augmentation of breast cancer development induced by lnc-LUCAT1 over-expression. In addition, SOX2 acted as a target of miR-7-5p. SOX2 was an oncogene in breast cancer through promoting cell proliferation, migration and invasion. The in vivo study confirmed the role of lnc-LUCAT1 in promoting tumor growth, accompanied with down-regulated SOX2 expression, whereas up-regulated miR-7-5p. Collectively, the lnc-LUCAT1/miR-7-5p-SOX2 regulatory pathway might provide a new and effective therapeutic strategy to prevent breast cancer development.

摘要

乳腺癌仍然是全球肿瘤相关死亡的主要原因。导致乳腺癌进展的发病机制尚未完全阐明。越来越多的证据表明,长链非编码 RNA(lncRNA)与各种恶性肿瘤有关,包括乳腺癌。在本研究中,我们试图探讨 lncRNA-肺癌相关转录本 1(LUCAT1)在乳腺癌发生发展中的表达和作用。结果表明,lnc-LUCAT1 在乳腺癌组织和细胞系中表达明显上调。lnc-LUCAT1 的过表达增强了乳腺癌细胞系中的细胞增殖、迁移和侵袭。此外,发现 lnc-LUCAT1 是 miR-7-5p 的靶标。lnc-LUCAT1 与 miR-7-5p 呈负相关。lnc-LUCAT1 过表达增强诱导的乳腺癌发展需要减少 miR-7-5p。此外,SOX2 是 miR-7-5p 的靶标。SOX2 通过促进细胞增殖、迁移和侵袭,是乳腺癌的致癌基因。体内研究证实了 lnc-LUCAT1 在促进肿瘤生长中的作用,同时伴有 SOX2 表达下调,而 miR-7-5p 表达上调。总之,lnc-LUCAT1/miR-7-5p-SOX2 调控途径可能为预防乳腺癌发展提供一种新的有效治疗策略。

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