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长链非编码 RNA LINC00173 通过抑制 miR-490-3p 的表达促进三阴性乳腺癌的进展。

LncRNA LINC00173 enhances triple-negative breast cancer progression by suppressing miR-490-3p expression.

机构信息

Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

出版信息

Biomed Pharmacother. 2020 May;125:109987. doi: 10.1016/j.biopha.2020.109987. Epub 2020 Feb 10.

DOI:10.1016/j.biopha.2020.109987
PMID:32058222
Abstract

Long non-coding RNA (lncRNA) LINC00173 has been previously shown to promote chemoresistance and progression of small-cell lung cancer. Herein, we examine the clinical significance and biological function of LINC00173 in triple-negative breast cancer (TNBC). Quantitative PCR analysis was performed to determine the expression of LINC00173 in TNBC and adjacent breast tissues (n = 84). The associations of LINC00173 expression with cancer features and survival of TNBC patients were analyzed. The function of LINC00173 in TNBC cell proliferation, colony formation, and invasion was explored. TNBCs expressed increased levels of LINC00173 relative to normal breast tissues. TNBC patients with high tumoral LINC00173 levels had a lower recurrence-free survival and overall survival rate than those with low LINC00173 expression. Silencing of LINC00173 inhibited the proliferation, colony formation, and invasion of TNBC cells, whereas overexpression of LINC00173 exerted opposite effects. In vivo studies confirmed the reduction of tumor growth by LINC00173 depletion. Mechanistic investigation revealed that LINC00173 suppressed miR-490-3p to promote aggressive phenotype in TNBC cells. There was an inverse correlation between miR-490-3p and LINC00173 in TNBC (r = -0.2647, P =  0.0149). Altogether, LINC00173 functions as an oncogene in TNBC through antagonization of miR-490-3p. Upregulation of LINC00173 is associated with poor prognosis in TNBC. Targeting LINC00173 provides a potential therapeutic strategy for TNBC.

摘要

长链非编码 RNA(lncRNA)LINC00173 先前被证明可促进小细胞肺癌的化疗耐药和进展。在此,我们研究了 LINC00173 在三阴性乳腺癌(TNBC)中的临床意义和生物学功能。通过定量 PCR 分析确定了 LINC00173 在 TNBC 和相邻乳腺组织中的表达(n=84)。分析了 LINC00173 表达与 TNBC 患者癌症特征和生存的关联。探讨了 LINC00173 在 TNBC 细胞增殖、集落形成和侵袭中的功能。与正常乳腺组织相比,TNBC 表达更高水平的 LINC00173。LINC00173 高表达的 TNBC 患者比 LINC00173 低表达的患者复发无进展生存率和总生存率更低。沉默 LINC00173 抑制了 TNBC 细胞的增殖、集落形成和侵袭,而过表达 LINC00173 则产生相反的效果。体内研究证实了 LINC00173 耗竭可减少肿瘤生长。机制研究表明,LINC00173 通过抑制 miR-490-3p 促进 TNBC 细胞的侵袭表型。在 TNBC 中,miR-490-3p 与 LINC00173 呈负相关(r=-0.2647,P=0.0149)。总之,LINC00173 通过拮抗 miR-490-3p 在 TNBC 中发挥癌基因作用。LINC00173 的上调与 TNBC 的不良预后相关。靶向 LINC00173 为 TNBC 提供了一种潜在的治疗策略。

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