MicroRNA-34a inhibits the proliferation and promotes the apoptosis of non-small cell lung cancer H1299 cell line by targeting TGFβR2
MicroRNA-34a inhibits the proliferation and promotes the apoptosis of non-small cell lung cancer H1299 cell line by targeting TGFβR2
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MicroRNA-34a 通过靶向 TGFβR2 抑制非小细胞肺癌 H1299 细胞系的增殖并促进其凋亡
DOI：
10.1007/s13277-014-2861-5
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发表时间：
2015-04-01
期刊：
影响因子：
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通讯作者：
Jin, You-Xin
中科院分区：
文献类型：
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作者：
Ma, Zhong-Liang;Hou, Pin-Pin;Jin, You-Xin
MicroRNA（MiRNAs）是一类非编码RNA小分子，通过与靶信使RNA（mRNA）的3 '-非翻译区（3'-UTR）结合，在转录后基因表达中起重要调控作用。在这项研究中，我们分析了miRNA-34 a（miR-34 a）作为非小细胞肺癌（NSCLC）H1299细胞系的肿瘤抑制因子。miR-34 a在4种不同的NSCLC细胞系H1299、A549、SPCA-1和HCC 827中的表达水平显著低于非致瘤性支气管上皮细胞系BEAS-2B。在人NSCLC组织中，与pT 1组相比，pT 2 -4组的miR-34 a表达水平也显著降低。miR-34 a模拟物可抑制H1299细胞的增殖并诱导细胞凋亡。荧光素酶分析显示，miR-34 a通过靶向TGF β R2 mRNA的3 '-UTR中的一个结合位点来抑制TGF β R2表达。定量实时PCR（qRT-PCR）和蛋白质印迹分析证实，miR-34 a在mRNA和蛋白质水平均降低TGF β R2表达。此外，通过siRNA下调TGF β R2在H1299细胞中显示出与miR-34 a模拟物相同的增殖和凋亡效果。结果表明，miR-34 a可抑制H1299细胞增殖，促进细胞凋亡，其机制可能与下调其靶基因TGF β R2有关。
MicroRNAs (MiRNAs) are small non-coding RNA molecules which act as important regulators of post-transcriptional gene expression by binding 3'-untranslated region (3'-UTR) of target messenger RNA (mRNA). In this study, we analyzed miRNA-34a (miR-34a) as a tumor suppressor in non-small cell lung cancer (NSCLC) H1299 cell line. The expression level of miR-34a in four different NSCLC cell lines, H1299, A549, SPCA-1, and HCC827, was significantly lower than that in the non-tumorigenic bronchial epithelium cell line BEAS-2B. In human NSCLC tissues, miR-34a expression level was also significantly decreased in pT2-4 compared with the pT1 group. Moreover, miR-34a mimic could inhibit the proliferation and triggered apoptosis in H1299 cells. Luciferase assays revealed that miR-34a inhibited TGF beta R2 expression by targeting one binding site in the 3'-UTR of TGF beta R2 mRNA. Quantitative real-time PCR (qRT-PCR) and Western blot assays verified that miR-34a reduced TGF beta R2 expression at both mRNA and protein levels. Furthermore, downregulation of TGF beta R2 by siRNA showed the same effects on the proliferation and apoptosis as miR-34a mimic in H1299 cells. Our results demonstrated that miR-34a could inhibit the proliferation and promote the apoptosis of H1299 cells partially through the downregulation of its target gene TGF beta R2.