Anillin is required for tumor growth and regulated by miR-15a/miR-16-1 in HBV-related hepatocellular carcinoma.
Anillin is required for tumor growth and regulated by miR-15a/miR-16-1 in HBV-related hepatocellular carcinoma.
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在 HBV 相关肝细胞癌中，Anillin 是肿瘤生长所必需的，并受 miR-15a/miR-16-1 调节
DOI：
10.18632/aging.101510
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发表时间：
2018-08-09
期刊：
影响因子：
--
通讯作者：
Huang YH
中科院分区：
文献类型：
--
作者：
Lian YF;Huang YL;Wang JL;Deng MH;Xia TL;Zeng MS;Chen MS;Wang HB;Huang YH
苯胺醛（ANLN）是一种肌动蛋白结合蛋白，在胞质分裂过程中对卵裂沟的组装至关重要。虽然据报道在各种人类癌症中过表达，但其在肝细胞癌（HCC）中的作用尚不清楚。为了解决这一问题，我们证实，在436例手术切除的HCC组织中，通过免疫组织化学、实时定量PCR和蛋白质印迹法检测到肿瘤组织中ANLN表达高于邻近的HCC非肿瘤组织。相关分析和Kaplan-Meier分析显示，ANLN表达越高，患者的临床结局越差，生存时间越短。此外，ANLN抑制导致生长抑制，减少集落形成，和较低的球数在悬浮培养。从机制上讲，ANLN缺陷诱导了沿着凋亡信号和DNA损伤检查点的激活的多核细胞数量的增加。此外，HBV感染通过抑制microRNA（miR）-15 a和miR-16-1的表达来增加ANLN表达，这两种基因均通过靶向其3'非翻译区而被鉴定为ANLN上游阻遏物。因此，我们得出结论，ANLN促进肿瘤生长的方式减少细胞凋亡和DNA损伤。ANLN的表达水平显著影响HCC患者的生存概率，并可能代表一种有前途的预后生物标志物。
Anillin (ANLN) is an actin-binding protein essential for assembly of cleavage furrow during cytokinesis. Although reportedly overexpressed in various human cancers, its role in hepatocellular carcinoma (HCC) is unclear. To address this issue, we confirmed that in 436 liver samples obtained from surgically removed HCC tissues, higher ANLN expression was detected in tumor tissues than in adjacent non-tumor tissues of HCC as measured by immunohistochemistry, quantitative real-time PCR and western blotting. Correlation and Kaplan-Meier analysis revealed that patients with higher ANLN expression were associated with worse clinical outcomes and a shorter survival time, respectively. Moreover, ANLN inhibition resulted in growth restraint, reduced colony formation, and a lower sphere number in suspension culture. Mechanistically, ANLN deficiency induced an increasing number of multinucleated cells along with the activation of apoptosis signaling and DNA damage checkpoints. Furthermore, HBV infection increased ANLN expression by inhibiting the expression of microRNA (miR)-15a and miR-16-1, both of which were identified as ANLN upstream repressors by targeting its 3’ untranslated region. Thus, we conclude that ANLN promotes tumor growth by ways of decreased apoptosis and DNA damage. Expression level of ANLN significantly influences the survival probability of HCC patients and may represent a promising prognostic biomarker.
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影响因子：
3.8
作者：
Magnusson K;Gremel G;Rydén L;Pontén V;Uhlén M;Dimberg A;Jirström K;Pontén F
通讯作者：
Pontén F
影响因子：
11.2
作者：
Suzuki, C;Daigo, Y;Nakamura, Y
通讯作者：
Nakamura, Y
影响因子：
3.8
作者：
Anaya, Jordan
通讯作者：
Anaya, Jordan
影响因子：
4.6
作者：
Field, CM;Coughlin, M;Sullivan, W
通讯作者：
Sullivan, W
影响因子：
4.3
作者：
Hai, Hoang;Tamori, Akihiro;Kawada, Norifumi
通讯作者：
Kawada, Norifumi