SIRT2, a direct target of miR-212-5p, suppresses the proliferation and metastasis of colorectal cancer cells.
SIRT2, a direct target of miR-212-5p, suppresses the proliferation and metastasis of colorectal cancer cells.
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DOI：
10.1111/jcmm.15603
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发表时间：
2020-09
影响因子：
5.3
通讯作者：
Wu W
中科院分区：
文献类型：
--
作者：
Du F;Li Z;Zhang G;Shaoyan S;Geng D;Tao Z;Qiu K;Liu S;Zhou Y;Zhang Y;Gu J;Wang G;Li L;Wu W
人类sirtuin 2(SIRT2)在多种类型的肿瘤中均有异常表达，但SIRT2在结直肠癌中的作用、机制及临床意义尚不清楚。本研究结果表明，与配对的正常组织相比，SIRT2在结直肠癌组织中的表达显著降低。SIRT2基因缺失与临床病理特征相关，包括远处转移、淋巴结转移和美国癌症联合委员会(AJCC)分期，可作为判断结直肠癌患者预后不良的独立因素。进一步的功能获得和功能丧失分析表明，SIRT2在体内和体外都抑制了结直肠癌细胞的增殖和转移。从机制上讲，miR-212-5p直接靶向SIRT2 3‘-非翻译区，导致SIRT2下调。SIRT2的异位表达逆转了miR-212-5p过表达对结直肠癌细胞集落形成、侵袭、迁移和增殖的影响。临床上，miR-212-5p与SIRT2表达呈负相关。在结直肠癌患者中，miR-212-5p的高表达导致预后不良和侵袭性的临床病理特征。综上所述，这些结果表明，miR-212-5p靶向的SIRT2在结直肠癌中发挥肿瘤抑制作用，miR-212-5p/SIRT2轴在结直肠癌中是一个有前景的预后因素和潜在的治疗靶点。
The aberrant expression of human sirtuin 2 (SIRT2) has been detected in various types of cancer; however, the biological roles, underlying mechanisms and clinical significance of SIRT2 dysregulation in human colorectal cancer (CRC) remain unclear. The results of this study demonstrate that compared with paired normal tissues, SIRT2 expression is significantly decreased in CRC tissues. SIRT2 loss has been correlated with clinicopathological characteristics, including distant metastasis, lymph node metastasis and American Joint Committee on Cancer (AJCC) stage; this loss serves as an independent factor that indicates a poor prognosis for patients with CRC. Further gain‐ and loss‐of‐function analyses have demonstrated that SIRT2 suppresses CRC cell proliferation and metastasis both in vivo and in vitro. Mechanistically, miR‐212‐5p was identified to directly target the SIRT2 3′‐untranslated region (3′‐UTR), leading to SIRT2 down‐regulation. The ectopic expression of SIRT2 reverses the effect of miR‐212‐5p overexpression on CRC cell colony formation, invasion, migration and proliferation. Clinically, an inverse correlation was found between miR‐212‐5p and SIRT2 expression. High miR‐212‐5p expression has been found to result in a poor prognosis and aggressive clinicopathological characteristics in patients with CRC. Taken together, these results suggest that SIRT2, targeted by miR‐212‐5p, acts as a tumour suppressor in CRC and that the miR‐212‐5p/SIRT2 axis is a promising prognostic factor and potential therapeutic target in CRC.
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影响因子：
11.2
作者：
Fiskus W;Coothankandaswamy V;Chen J;Ma H;Ha K;Saenz DT;Krieger SS;Mill CP;Sun B;Huang P;Mumm JS;Melnick AM;Bhalla KN
通讯作者：
Bhalla KN
影响因子：
64.5
作者：
Kugel S;Sebastián C;Fitamant J;Ross KN;Saha SK;Jain E;Gladden A;Arora KS;Kato Y;Rivera MN;Ramaswamy S;Sadreyev RI;Goren A;Deshpande V;Bardeesy N;Mostoslavsky R
通讯作者：
Mostoslavsky R
PGK1乙酰化促进肝癌细胞增殖和肿瘤发生
影响因子：
13.5
作者：
Hu, Hongli;Zhu, Wenwei;Gao, Daming
通讯作者：
Gao, Daming
SIRT2 通过损害 Skp2 介导的 p27 降解抑制非小细胞肺癌细胞生长
影响因子：
--
作者：
Li Z;Huang J;Yuan H;Chen Z;Luo Q;Lu S
通讯作者：
Lu S
SIRT1介导的SOX2转录调控对肝癌干细胞的自我更新具有重要意义
影响因子：
13.5
作者：
Liu, Limei;Liu, Chungang;Qian, Cheng
通讯作者：
Qian, Cheng