MiR-34a/c-Dependent PDGFR-α/β Downregulation Inhibits Tumorigenesis and Enhances TRAIL-Induced Apoptosis in Lung Cancer.
MiR-34a/c-Dependent PDGFR-α/β Downregulation Inhibits Tumorigenesis and Enhances TRAIL-Induced Apoptosis in Lung Cancer.
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DOI：
10.1371/journal.pone.0067581
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Croce CM
中科院分区：
文献类型：
--
作者：
Garofalo M;Jeon YJ;Nuovo GJ;Middleton J;Secchiero P;Joshi P;Alder H;Nazaryan N;Di Leva G;Romano G;Crawford M;Nana-Sinkam P;Croce CM
肺癌是当今世界癌症死亡的主要原因。尽管在肺癌治疗方面取得了一些进展，但患者的存活率仍然很低。在人类恶性肿瘤中，microRNAs(MiRNAs)可作为癌基因或抑癌基因。MiR-34家族由抑制肿瘤的miRNAs组成，已有报道其在包括非小细胞肺癌(NSCLC)在内的多种癌症中表达降低。在这项研究中，我们发现miR-34a和miR-34c靶向于血小板衍生生长因子受体α和β(PDGFR-α和PDGFR-β)，这是一种诱导肿瘤增殖、迁移和侵袭的细胞表面酪氨酸激酶受体。与正常组织相比，miR-34a和miR-34c在肺癌组织中表达下调。此外，我们还发现肺肿瘤组织中PDGFR-α/β和miR-34a/c的表达呈负相关。最后，miR-34a/c过表达或siRNAs下调PDGFR-α/β，强烈增强了对肿瘤坏死因子相关的凋亡诱导配体(TRAIL)的反应，同时降低了非小细胞肺癌细胞的迁移和侵袭能力。
Lung cancer is the leading cause of cancer mortality in the world today. Although some advances in lung cancer therapy have been made, patient survival is still poor. MicroRNAs (miRNAs) can act as oncogenes or tumor-suppressor genes in human malignancy. The miR-34 family consists of tumor-suppressive miRNAs, and its reduced expression has been reported in various cancers, including non-small cell lung cancer (NSCLC). In this study, we found that miR-34a and miR-34c target platelet-derived growth factor receptor alpha and beta (PDGFR-α and PDGFR-β), cell surface tyrosine kinase receptors that induce proliferation, migration and invasion in cancer. MiR-34a and miR-34c were downregulated in lung tumors compared to normal tissues. Moreover, we identified an inverse correlation between PDGFR-α/β and miR-34a/c expression in lung tumor samples. Finally, miR-34a/c overexpression or downregulation of PDGFR-α/β by siRNAs, strongly augmented the response to TNF-related apoptosis inducing ligand (TRAIL) while reducing migratory and invasive capacity of NSCLC cells.
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影响因子：
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通讯作者：
Croce CM