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微小 RNA-193a-3p 和 -5p 通过下调 ERBB4/PIK3R3/mTOR/S6K2 信号通路抑制人非小细胞肺癌的转移。

MicroRNA-193a-3p and -5p suppress the metastasis of human non-small-cell lung cancer by downregulating the ERBB4/PIK3R3/mTOR/S6K2 signaling pathway.

机构信息

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Oncogene. 2015 Jan 22;34(4):413-23. doi: 10.1038/onc.2013.574. Epub 2014 Jan 27.


DOI:10.1038/onc.2013.574
PMID:24469061
Abstract

The metastatic cascade is a complex and multistep process with many potential barriers. Recent evidence has shown that microRNAs (miRNAs) are involved in carcinogenesis and tumor progression in non-small-cell lung cancer (NSCLC). In this study, by comparing the miRNA expression profiles of SPC-A-1sci (high metastatic) and SPC-A-1 (weakly metastatic) cells, we demonstrated that the downregulation and function of miR-193a-3p and miR-193a-5p in NSCLC metastasis and the expression of these miRNAs was suppressed in NSCLC compared with corresponding non-tumorous tissues. Decreased miR-193a-3p/5p expression was significantly associated with tumor node metastasis (TNM) and lymph node metastasis. Furthermore, functional assays showed that the overexpression of miR-193a-3p/5p inhibited NSCLC cell migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and lung metastasis formation in vivo. In addition, we discovered that ERBB4 and S6K2 were the direct targets of miR-193a-3p and that PIK3R3 and mTOR were the direct targets of miR-193a-5p in NSCLC. We also observed that miR-193a-3p/5p could inactivate the AKT/mTOR signaling pathway. Thus, miR-193a-3p/5p functions as a tumor suppressor and has an important role in NSCLC metastasis through ERBB signaling pathway.

摘要

转移级联是一个复杂的多步骤过程,有许多潜在的障碍。最近的证据表明,microRNAs(miRNAs)参与非小细胞肺癌(NSCLC)的癌变和肿瘤进展。在这项研究中,通过比较 SPC-A-1sci(高转移性)和 SPC-A-1(弱转移性)细胞的 miRNA 表达谱,我们证明了 miR-193a-3p 和 miR-193a-5p 在 NSCLC 转移中的下调和功能,以及这些 miRNA 在 NSCLC 中的表达与相应的非肿瘤组织相比受到抑制。miR-193a-3p/5p 表达的降低与肿瘤淋巴结转移(TNM)和淋巴结转移显著相关。此外,功能测定表明,miR-193a-3p/5p 的过表达抑制了 NSCLC 细胞在体外的迁移、侵袭和上皮间质转化(EMT),以及体内的肺转移形成。此外,我们发现 ERBB4 和 S6K2 是 miR-193a-3p 的直接靶标,而 PIK3R3 和 mTOR 是 miR-193a-5p 在 NSCLC 中的直接靶标。我们还观察到 miR-193a-3p/5p 可以使 AKT/mTOR 信号通路失活。因此,miR-193a-3p/5p 作为一种肿瘤抑制因子,通过 ERBB 信号通路在 NSCLC 转移中发挥重要作用。

相似文献

[1]
MicroRNA-193a-3p and -5p suppress the metastasis of human non-small-cell lung cancer by downregulating the ERBB4/PIK3R3/mTOR/S6K2 signaling pathway.

Oncogene. 2014-1-27

[2]
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[3]
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[4]
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J Biol Chem. 2015-1-9

[5]
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[6]
The microRNA-130a-5p/RUNX2/STK32A network modulates tumor invasive and metastatic potential in non-small cell lung cancer.

BMC Cancer. 2020-6-22

[7]
MiR-193a-3p is an Important Tumour Suppressor in Lung Cancer and Directly Targets KRAS.

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[8]
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[9]
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[10]
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Eur Rev Med Pharmacol Sci. 2018-4

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[4]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Predicting 2-year survival for radiation regimens in advanced non-small cell lung cancer.

Clin Oncol (R Coll Radiol). 2013-8-17

[2]
Glypican-5 is a novel metastasis suppressor gene in non-small cell lung cancer.

Cancer Lett. 2013-8-17

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MicroRNA-31 predicts the presence of lymph node metastases and survival in patients with lung adenocarcinoma.

Clin Cancer Res. 2013-8-14

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Quantitative proteomic analysis identifies CPNE3 as a novel metastasis-promoting gene in NSCLC.

J Proteome Res. 2013-6-6

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MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1.

Nat Commun. 2013

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ERBB4 confers metastatic capacity in Ewing sarcoma.

EMBO Mol Med. 2013-5-16

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miR-194 suppresses metastasis of non-small cell lung cancer through regulating expression of BMP1 and p27(kip1).

Oncogene. 2013-4-15

[8]
Reduction of the ST6 β-galactosamide α-2,6-sialyltransferase 1 (ST6GAL1)-catalyzed sialylation of nectin-like molecule 2/cell adhesion molecule 1 and enhancement of ErbB2/ErbB3 signaling by microRNA-199a.

J Biol Chem. 2013-3-15

[9]
miR-612 suppresses the invasive-metastatic cascade in hepatocellular carcinoma.

J Exp Med. 2013-3-11

[10]
Inherited variation in miR-290 expression suppresses breast cancer progression by targeting the metastasis susceptibility gene Arid4b.

Cancer Res. 2013-2-27

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