microRNA-874 suppresses tumor proliferation and metastasis in hepatocellular carcinoma by targeting the DOR/EGFR/ERK pathway.
microRNA-874 suppresses tumor proliferation and metastasis in hepatocellular carcinoma by targeting the DOR/EGFR/ERK pathway.
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microRNA-874通过靶向DOR/EGFR/ERK通路抑制肝细胞癌的肿瘤增殖和转移
DOI：
10.1038/s41419-017-0131-3
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发表时间：
2018-01-26
影响因子：
9
通讯作者：
Tang B
中科院分区：
文献类型：
--
作者：
Zhang Y;Wei Y;Li X;Liang X;Wang L;Song J;Zhang X;Zhang C;Niu J;Zhang P;Ren Z;Tang B
δ阿片受体（DOR）参与肝细胞癌（HCC）恶性转化和肿瘤进展的调控。然而，HCC中DOR的调节仍然不清楚。我们发现miR-874被鉴定为DOR的负调控因子，DOR是miR-874通过其3′非翻译区（UTR）的直接和功能性靶点。此外，miR-874在HCC中下调，其表达与DOR表达呈负相关。miR-874的下调也与较大的肿瘤大小、更多的血管浸润、较差的TNM分期、较差的肿瘤分化和较差的患者预后相关。在功能上，miR-874在HCC细胞系SK-hep-1中的过表达抑制细胞生长、迁移、体外侵袭和体内致瘤性。此外，miR-874过表达抑制DOR，导致表皮生长因子受体（EGFR）和细胞外信号调节激酶（ERK）磷酸化下调。EGFR激活剂-表皮生长因子（EGF）-可以拯救由miR-874过表达诱导的增殖和迁移抑制，并且EGF的拯救作用被ERK抑制剂阻断。我们的研究结果提示，miRNA-874是DOR的负调控因子，通过靶向DOR/EGFR/ERK通路抑制肝癌的增殖和转移，可能成为肝癌治疗的潜在靶点。
The δ opioid receptor (DOR) is involved in the regulation of malignant transformation and tumor progression of hepatocellular carcinoma (HCC). However, regulation of the DOR in HCC remains poorly defined. We found that miR-874 was identified as a negative regulator of the DOR, which is a direct and functional target of miR-874 via its 3′ untranslated region (UTR). Moreover, miR-874 was downregulated in HCC and its expression was inversely correlated with DOR expression. Downregulation of miR-874 was also associated with larger tumor size, more vascular invasion, a poor TNM stage, poor tumor differentiation, and inferior patient outcomes. Functionally, overexpression of miR-874 in the HCC cell line SK-hep-1 inhibited cell growth, migration, in vitro invasion, and in vivo tumorigenicity. Furthermore, miR-874 overexpression suppressed the DOR, resulting in a downregulated epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase (ERK) phosphorylation. The EGFR activator—epidermal growth factor (EGF)—can rescue the proliferation and migration suppression induced by miR-874 overexpression, and the rescue effects of the EGF were blocked by an ERK inhibitor. Our study results suggest that miRNA-874 is a negative regulator of the DOR that can suppress tumor proliferation and metastasis in HCC by targeting the DOR/EGFR/ERK pathway, which may be a potential target for HCC treatment.
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影响因子：
3.7
作者：
Chen HF;Lan CY
通讯作者：
Lan CY
MicroRNA-874 通过靶向 CDK9 抑制人乳腺癌细胞增殖并诱导细胞凋亡
影响因子：
3.5
作者：
Wang, Ling;Gao, Wen;Wang, Fuqiang
通讯作者：
Wang, Fuqiang
影响因子：
4.7
作者：
Nicoll, J;Axiotis, CA;Bergasa, NV
通讯作者：
Bergasa, NV
影响因子：
4.2
作者：
Han, Jinfeng;Liu, Zhongmin;Pan, Weiyun
通讯作者：
Pan, Weiyun
microRNA 在翻译调控和癌症中的作用。
DOI：
10.4331/wjbc.v8.i1.45
发表时间：
2017-02-26
期刊：
World journal of biological chemistry
影响因子：
--
作者：
Oliveto S;Mancino M;Manfrini N;Biffo S
通讯作者：
Biffo S