The tumor suppressor miR-138-5p targets PD-L1 in colorectal cancer.
The tumor suppressor miR-138-5p targets PD-L1 in colorectal cancer.
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结直肠癌中肿瘤抑制因子 miR-138-5p 靶向 PD-L1
DOI：
10.18632/oncotarget.9659
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发表时间：
2016-07-19
期刊：
影响因子：
--
通讯作者：
Shen S
中科院分区：
文献类型：
--
作者：
Zhao L;Yu H;Yi S;Peng X;Su P;Xiao Z;Liu R;Tang A;Li X;Liu F;Shen S
microRNA（miRNAs）在癌症的发生和发展中起着关键作用。本研究探讨了miR-138- 5 p在人类结直肠癌（CRC）发展中的作用。miR-138- 5 p在结直肠癌组织中频繁下调，并与晚期临床分期、淋巴结转移和总生存率低相关。我们发现miR-138- 5 p通过与程序性细胞死亡配体1（PD-L1）3′非翻译区相互作用降低PD-L1的表达。miR-138- 5 p还在体外显著抑制CRC细胞生长并在体内抑制肿瘤发生。在人类CRC肿瘤中，PD-L1和miR-138- 5 p水平呈负相关，并且miR-138- 5 p抑制肿瘤模型中PD-L1的表达。这些结果表明，miR-138- 5 p是CRC中的肿瘤抑制因子，其作用至少部分通过PD-L1下调发挥。低miR-138- 5 p和高PD-L1水平与较短的CRC患者总体生存期相关，表明miR-138- 5 p和PD-L1可作为CRC生物标志物用于风险组分配、最佳治疗选择和临床结局预测。靶向PD-L1，可能通过施用miR-138- 5 p模拟物，可能是临床上有效的抗CRC治疗策略。
microRNAs (miRNAs) play critical roles in cancer development and progression. This study investigated the effects of miR-138-5p in human colorectal cancer (CRC) development. miR-138-5p was frequently downregulated in CRC tissues and was associated with advanced clinical stage, lymph node metastasis and poor overall survival. We found that miR-138-5p decreased expression of programmed cell death ligand 1 (PD-L1) through interaction with its PD-L1 3′ untranslated region. miR-138-5p also dramatically suppressed CRC cell growth in vitro and inhibited tumorigenesis in vivo. PD-L1 and miR-138-5p levels were inversely correlated in human CRC tumors, and miR-138-5p inhibited PD-L1 expression in tumor models. These results suggest that miR-138-5p is a tumor suppressor in CRC, and its effects are exerted at least partially through PD-L1 downregulation. Low miR-138-5p and high PD-L1 levels correlated with shorter overall CRC patient survival, indicating that miR-138-5p and PD-L1 may serve as CRC biomarkers for risk group assignment, optimal therapy selection and clinical outcome prediction. Targeting PD-L1, possibly by administering miR-138-5p mimics, might be a clinically effective anti-CRC therapeutic strategy.
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影响因子：
7.2
作者：
Peng W;Lizée G;Hwu P
通讯作者：
Hwu P
影响因子：
--
作者：
Darb-Esfahani S;Kunze CA;Kulbe H;Sehouli J;Wienert S;Lindner J;Budczies J;Bockmayr M;Dietel M;Denkert C;Braicu I;Jöhrens K
通讯作者：
Jöhrens K
影响因子：
8.4
作者：
Droeser, Raoul A.;Hirt, Christian;Tornillo, Luigi
通讯作者：
Tornillo, Luigi
影响因子：
11.5
作者：
Konishi, J;Yamazaki, K;Nishimura, M
通讯作者：
Nishimura, M
影响因子：
11.5
作者：
Ohigashi, Y;Sho, M;Nakajima, Y
通讯作者：
Nakajima, Y