LncRNA LINC00173 enhances triple-negative breast cancer progression by suppressing miR-490-3p expression
LncRNA LINC00173 enhances triple-negative breast cancer progression by suppressing miR-490-3p expression
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DOI：
10.1016/j.biopha.2020.109987
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发表时间：
2020-05-01
影响因子：
7.5
通讯作者：
Li, Xingya
中科院分区：
文献类型：
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作者：
Fan, Huijie;Yuan, Jing;Li, Xingya
长链非编码RNA (lncRNA) LINC00173先前已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。采用定量PCR方法检测LINC00173在TNBC及癌旁乳腺组织中的表达（n = 84）。分析LINC00173表达与TNBC患者肿瘤特征及生存的关系。探讨了LINC00173在TNBC细胞增殖、集落形成和侵袭中的作用。与正常乳腺组织相比，tnbc表达的LINC00173水平升高。肿瘤LINC00173高表达的TNBC患者的无复发生存率和总生存率低于低表达的患者。沉默LINC00173抑制TNBC细胞的增殖、集落形成和侵袭，而过表达LINC00173则发挥相反的作用。体内研究证实，LINC00173耗竭可减少肿瘤生长。机制研究显示，LINC00173抑制miR-490-3p促进TNBC细胞的侵袭性表型。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中发挥癌基因的作用。LINC00173的上调与TNBC的不良预后相关。靶向LINC00173为TNBC提供了潜在的治疗策略。
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.