miR-22 is down-regulated in gastric cancer, and its overexpression inhibits cell migration and invasion via targeting transcription factor Sp1
miR-22 is down-regulated in gastric cancer, and its overexpression inhibits cell migration and invasion via targeting transcription factor Sp1
复制标题
miR-22在胃癌中下调，其过表达通过靶向转录因子Sp1抑制细胞迁移和侵袭
DOI：
10.1007/s12032-013-0542-7
复制
发表时间：
2013-06-01
期刊：
影响因子：
3.4
通讯作者：
Liao, Cheng-Gong
中科院分区：
文献类型：
--
作者：
Guo, Mei-Mei;Hu, Li-Hua;Liao, Cheng-Gong
越来越多的证据表明，microRNA参与了癌症发生和发展的多个过程。最近，miR-22已被鉴定为许多人类癌症中的肿瘤抑制microRNA。然而，miR-22在胃癌中的具体功能目前尚不清楚。本研究首先采用实时荧光定量RT-PCR方法检测了30对胃癌组织和配对正常组织、2对正常组织和6对胃癌细胞系中miR-22的表达水平。我们发现miR-22在胃癌组织和胃癌细胞系中的表达均明显低于正常对照组。转染miR-22表达质粒可明显抑制胃癌细胞系SGC-7901和NCL-N87的迁移和侵袭能力。此外，我们还通过荧光素酶报告基因检测发现，Sp1在转录后水平受到miR-22的负调控。胃癌组织中Sp1的表达与miR-22的表达呈负相关，siRNA敲低Sp1可抑制胃癌细胞的恶性行为。因此，我们的研究结果表明，miR-22通过靶向Sp1基因并抑制胃癌细胞的迁移和侵袭而发挥肿瘤抑制作用。本研究的发现有助于目前对miR-22在胃癌中的功能的理解。
Accumulating evidence has shown that microRNAs are involved in multiple processes in cancer development and progression. Recently, miR-22 has been identified as a tumor-suppressing microRNA in many human cancers. However, the specific function of miR-22 in gastric cancer is unclear at this point. In this study, we first measured miR-22 expression level in 30 pairs of gastric cancer and matched normal tissues, two normal and six gastric cancer cell lines by real-time quantitative RT-PCR. We found that the expression of miR-22 in gastric cancer tissues and cell lines was much lower than that in normal control, respectively. Transfection of miR-22 expression plasmid could significantly inhibit the cell migration and invasion in SGC-7901 and NCL-N87 gastric cancer cell lines. Moreover, we also showed that Sp1 was negatively regulated by miR-22 at the posttranscriptional level, via a specific target site within the 3′UTR by luciferase reporter assay. The expression of Sp1 was inversely correlated with miR-22 expression in gastric cancer tissues, and knockdown of Sp1 by siRNA inhibited cell malignant behaviors. Thus, our findings suggest that miR-22 acts as tumor suppressor by targeting the Sp1 gene and inhibiting gastric cancer cell migration and invasion. The findings of this study contribute to current understanding of the functions of miR-22 in gastric cancer.