E2F8, a direct target of miR-144, promotes papillary thyroid cancer progression via regulating cell cycle.
E2F8, a direct target of miR-144, promotes papillary thyroid cancer progression via regulating cell cycle.
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DOI：
10.1186/s13046-017-0504-6
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发表时间：
2017-03-07
期刊：
影响因子：
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通讯作者：
Su C
中科院分区：
文献类型：
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作者：
Sun J;Shi R;Zhao S;Li X;Lu S;Bu H;Ma X;Su C
甲状腺癌是最常见的内分泌系统恶性肿瘤，乳头状甲状腺癌(PTC)是最常见的亚型。E2F8是一个新发现的E2F家族成员，据报道与多种人类肿瘤的发生发展有关，但其在PTC中的临床意义和生物学作用尚不清楚。从肿瘤基因组图谱(TCGA)获得E2F8或miR-144在PTC组织中的表达谱，并分析E2F8表达与PTC临床病理特征的相关性。体外和体内观察E2F8和miR-144对细胞增殖的影响。荧光素酶报告实验确定E2F8是miR-144的直接靶点。E2F8在PTC组织中广泛上调，且E2F8的过度表达与PTC的临床病理特征密切相关。相反，我们发现在体内外，沉默的E2F8通过下调细胞周期蛋白D_1(CCND_1)而诱导细胞周期停滞，从而显著抑制PTC细胞的增殖。我们还鉴定了miR-144是一种肿瘤抑制的microRNA，它直接靶向E2F8在体内外抑制PTC细胞的增殖。此外，miR-144在PTC中广泛下调，其表达与E2F8表达呈负相关。我们的结果表明，一个新的miR-144/E2F8/CCND1调节轴控制着PTC的发展，这可能为PTC的预后和治疗提供潜在的策略。不适用。本文的在线版本(doi：10.1186/s13046-0170504-6)包含补充材料，授权用户可以使用。
Thyroid cancer is the most common malignancy of endocrine system, and papillary thyroid cancer (PTC) is the most common subtype. E2F8, a novel identified E2F family member, was reported to associate with progression of several human cancers, however, its clinical significance and biological role in PTC remain unknown. E2F8 or miR-144 expression profiles in PTC tissues were obtained from The Cancer Genome Atlas (TCGA) datasets, and the correlation of E2F8 expression with clinicopathological features was analyzed in a cohort PTC patients. The effects of E2F8 and miR-144 on proliferation were evaluated both in vitro and in vivo. Luciferase reporter assay was used to determine E2F8 was a direct target of miR-144. E2F8 was widely upregulated in PTC tissues, and overexpression of E2F8 was correlated with more aggressive clinicopathological features. In contrast, we found that silence of E2F8 significantly suppressed proliferation of PTC cells by inducing G1-phase arrest via downregulating Cyclin D1 (CCND1) both in vitro and in vivo. We also identified miR-144 as a tumor-suppressive microRNA that directly targeted E2F8 to inhibit proliferation of PTC cells in vitro and in vivo. Moreover, miR-144 was widely downregulated in PTC, where its expression correlated inversely with E2F8 expression. Our results demonstrate a new miR-144/E2F8/CCND1 regulatory axis controlling PTC development, which may offer a potential prognostic and therapeutic strategy. No applicable. The online version of this article (doi:10.1186/s13046-017-0504-6) contains supplementary material, which is available to authorized users.