Department of Thoracic Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuannanli, Chaoyang District, Beijing 100021, China.
Carcinogenesis. 2011 Jul;32(7):1025-32. doi: 10.1093/carcin/bgr078. Epub 2011 May 5.
Cyclin E is reported to be an important cell cycle regulator, and its dysregulation is implicated in tumorigenesis including esophageal squamous cell carcinoma (ESCC). MicroRNAs (miRNAs) regulate gene expression at the posttranscriptional level and play important roles in tumor initiation and progression. However, the regulation of cyclin E by miRNAs is still unclear in ESCC. In the present study, we found that overexpression of miR-29c inhibited cyclin E expression by targeting 3' untranslated region of cyclin E messenger RNA in ESCC cells. Moreover, overexpression of miR-29c induced cell cycle G(1)/G(0) arrest through suppression of cyclin E expression, without affecting other G(1) phase-related proteins level, such as cyclin D1, cyclin D2, cyclin dependent kinase (CDK) 2 and CDK6. Furthermore, we demonstrated that overexpression of miR-29c inhibited proliferation of ESCC cells in vitro and in vivo. In addition, we detected miR-29c expression in 26 pairs of esophageal tumor-in-site-tissues and 60 pairs of ESCC tissues. The result showed that miR-29c level significantly decreased in ESCC tumor tissues and cell lines compared with normal esophageal epithelia. Taken together, our findings indicated that miR-29c was frequently downregulated in ESCC tissues and cells and suppressed tumor growth by inducing cell cycle G(1)/G(0) arrest mainly through modulating cyclin E expression.
细胞周期蛋白 E 被报道为一种重要的细胞周期调节剂，其失调与包括食管鳞状细胞癌（ESCC）在内的肿瘤发生有关。MicroRNAs（miRNAs）在转录后水平调节基因表达，在肿瘤的发生和发展中发挥重要作用。然而，miRNAs 对 ESCC 中 cyclin E 的调节仍不清楚。在本研究中，我们发现 miR-29c 的过表达通过靶向 cyclin E mRNA 的 3'非翻译区抑制 ESCC 细胞中的 cyclin E 表达。此外，miR-29c 的过表达通过抑制 cyclin E 的表达诱导细胞周期 G1/G0 期阻滞，而不影响其他 G1 期相关蛋白水平，如 cyclin D1、cyclin D2、细胞周期蛋白依赖性激酶（CDK）2 和 CDK6。此外，我们证明 miR-29c 的过表达抑制了 ESCC 细胞在体外和体内的增殖。此外，我们检测了 26 对食管肿瘤原位组织和 60 对 ESCC 组织中的 miR-29c 表达。结果显示，与正常食管上皮相比，miR-29c 在 ESCC 肿瘤组织和细胞系中的水平显著降低。总之，我们的研究结果表明，miR-29c 在 ESCC 组织和细胞中经常下调，并通过主要调节 cyclin E 表达诱导细胞周期 G1/G0 期阻滞来抑制肿瘤生长。
