microRNA-21 promotes tumor proliferation and invasion in gastric cancer by targeting PTEN.
microRNA-21 promotes tumor proliferation and invasion in gastric cancer by targeting PTEN.
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DOI：
10.3892/or.2012.1645
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发表时间：
2012-04
期刊：
影响因子：
4.2
通讯作者：
Yan M
中科院分区：
文献类型：
--
作者：
Zhang BG;Li JF;Yu BQ;Zhu ZG;Liu BY;Yan M
胃癌是我国最常见的恶性肿瘤之一。microRNA是一类重要的非编码RNA，参与生物体的许多生物过程。microRNA-21（miR-21）已被确定为进一步研究的最合适的选择，因为它在几乎所有实体瘤中过表达;此外，已证明miR-21参与人类癌症的发生和发展。研究表明，PTEN是一种重要的肿瘤抑制因子，受多种miRNAs的调控。因此，本研究主要探讨miR-21在胃癌组织中的表达及其意义，以及miR-21在胃癌细胞生物学行为和PTEN表达中的作用。采用Real-time PCR方法检测胃癌组织、癌旁正常组织及胃癌细胞株中miR-21的表达。用pre-miR-21/miR-21抑制剂转染胃癌细胞系BGC-823，使miR-21过表达/下调。采用CCK-8试剂盒、流式细胞仪、划痕愈合试验和transwell试验评价miR-21对胃癌细胞生物学行为的影响。采用Western blotting和荧光素酶报告基因检测技术检测胃癌细胞系中miR-21表达下调后PTEN表达的变化。Real-time PCR分析显示，miR-21在胃癌组织中的表达高于癌旁组织。miR-21的表达与肿瘤组织的分化程度（P=0.004）、局部浸润和淋巴结转移有关（P<0.01）。转染后，pre-miR 21转染组BGC-823细胞生长速度明显快于阴性对照组和空白对照组（P<0.01）。miR-21表达下调对胃癌细胞的生物学行为有显著影响（P<0. 05）;划痕愈合实验显示转染前miR-21的胃癌细胞比对照细胞愈合更快，而transwell实验显示转染前miR-21的胃癌细胞在体外的迁移能力明显受到抑制（P<0. 05）。Western blot和荧光素酶报告基因检测结果显示，抑制miR-21后，PTEN的表达显著增加（P<0.05）。microRNA-21在胃癌组织中表达上调，且与肿瘤组织分化程度、局部浸润和淋巴结转移显著相关。miR-21过表达促进BGC-823细胞体外生长、侵袭和迁移，下调miR-21对胃癌细胞生物学行为的抑制作用更强;抑制miR-21可上调PTEN表达水平，提示PTEN可能是胃癌发生发展的靶基因。
Gastric cancer is one of the most common carcinomas in China. microRNAs, a type of non-coding RNA, are important specific regulators and are involved in numerous bioprocesses of an organism. microRNA-21 (miR-21) has been identified as the most suitable choice for further investigation because it is overexpressed in nearly all solid tumors; furthermore, it has been demonstrated that miR-21 is involved in the genesis and progression of human cancer. It has been reported that PTEN, an important tumour suppressor, is regulated by multiple miRNAs. Thus, in this study we focused on the expression and significance of miR-21 in gastric cancer tissues, and the role of miR-21 in the biological behaviour and the expression of PTEN in gastric cancer cells. Real-time PCR was used to detect miR-21 expression in gastric cancer tissues, the adjacent normal tissues, and the gastric cell lines. The gastric cancer cell line BGC-823 was transfected with pre-miR-21/miR-21 inhibitor to overexpress/downregulate miR-21. The influence of miR-21 on the biological behaviour of gastric cancer cells was evaluated using the CCK-8 kit, FCMs, the scratch healing assay and the transwell test. Western blotting and the Luciferase Reporter Assay were used to evaluate the change of PTEN expression after lowered expression of miR-21 in gastric cancer cell lines. Real-time PCR analysis indicated that miR-21 exhibited higher expression in gastric cancer tissues compared to the adjacent non-tumor tissues. miR-21 expression was significantly associated with the degree of differentiation of the tumour tissues (P=0.004), as well as local invasion and lymph node metastasis (P<0.01). After transfection, pre-miR21 BGC-823 cells grew faster than the negative and control groups (P<0.01). The reduction in miR-21 expression demonstrated a remarkable effect on the biological behaviour of gastric cancer cells (P<0.05); the pre-miR-21-transfected cells healed more quickly compared to the control cells in the scratch healing assay, whereas the transwell test indicated that cell migration in vitro was notably inhibited with the downregulation of miR-21 (P<0.05). The western blot results and Luciferase Reporter Assay demonstrated that PTEN expression was remarkably increased after miR-21 inhibition (P<0.05). microRNA-21 expression was upregulated in gastric carcinoma tissues and was significantly associated with the degree of differentiation of tumour tissues, local invasion and lymph node metastasis. Overexpression of miR-21 promoted BGC-823 cell growth, invasion and cell migration in vitro, whereas downregulation of miR-21 exhibited a stronger inhibitory effect on the biological behaviour of gastric cancer cells; additionally, miR-21 inhibition may upregulate the PTEN expression level, which indicates that PTEN may be a target gene for gastric cancer initiation and development.
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影响因子：
11.2
作者：
Wang P;Zou F;Zhang X;Li H;Dulak A;Tomko RJ Jr;Lazo JS;Wang Z;Zhang L;Yu J
通讯作者：
Yu J
影响因子：
4.3
作者：
To, MD;Perez-Losada, J;Balmain, A
通讯作者：
Balmain, A
影响因子：
8
作者：
Si, M.-L.;Zhu, S.;Mo, Y.-Y.
通讯作者：
Mo, Y.-Y.
影响因子：
11.2
作者：
Iorio, MV;Ferracin, M;Croce, CM
通讯作者：
Croce, CM
影响因子：
5
作者：
Xiao, Bingxiu;Guo, Junming;Zhong, Jiuchang
通讯作者：
Zhong, Jiuchang