Wang An-Ming, Huang Tzu-Ting, Hsu Kai-Wen, Huang Kuo-Hung, Fang Wen-Liang, Yang Muh-Hwa, Lo Su-Shun, Chi Chin-Wen, Lin Jing-Jer, Yeh Tien-Shun
Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei , Taiwan. Department of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei , Taiwan.
Department of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei , Taiwan. Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei , Taiwan. These authors contributed equally to this work.
Oncotarget. 2014 Jul 15;5(13):5002-16. doi: 10.18632/oncotarget.2073.
Gastric cancer is the second leading cause of cancer-related death worldwide. Herein, we investigated the role of transcription factor Yin Yang 1 (YY1), a multi-functional protein, in tumorigenesis of gastric cancer cells. Results showed that YY1 contributed to gastric carcinogenesis of SC-M1 cells including growth, viability, and abilities of colony formation, migration, invasion, and tumorsphere formation. Levels of pluripotency genes CD44, Oct4, SOX-2, and Nanog were also up-regulated by YY1 in SC-M1 cells. Additionally, the 3'-untranslated region (3'-UTR) of YY1 mRNA was the target of microRNA-34 (miR-34) family consisting of miR-34a, miR-34b, and miR-34c. Overexpression of miR-34 family suppressed carcinogenesis through down-regulation of YY1 in NUGC-3 gastric cancer cells scarcely expressing miR-34 family. Alternatively, knockdown of miR-34 family promoted tumorigenesis via up-regulation of YY1 in SC-M1 and AZ521 gastric cancer cells with higher levels of miR-34 family. The miR-34 family also affected tumorsphere ultra-structure and inhibited the xenografted tumor growth as well as lung metastasis of SC-M1 cells through YY1. Expressions of miR-34a and miR-34c in gastric cancer tissues of patients were lower than those in normal tissues. Taken together, these results suggest that miR-34 family-YY1 axis plays an important role in the control of gastric carcinogenesis.
胃癌是全球癌症相关死亡的第二大主要原因。在此，我们研究了多功能蛋白转录因子阴阳1（YY1）在胃癌细胞肿瘤发生中的作用。结果表明，YY1促进了SC-M1细胞的胃癌发生，包括生长、活力以及集落形成、迁移、侵袭和肿瘤球形成能力。YY1还上调了SC-M1细胞中多能性基因CD44、Oct4、SOX-2和Nanog的水平。此外，YY1 mRNA的3'非翻译区（3'-UTR）是由miR-34a、miR-34b和miR-34c组成的miR-34家族的靶标。在几乎不表达miR-34家族的NUGC-3胃癌细胞中，miR-34家族的过表达通过下调YY1抑制了肿瘤发生。相反，在miR-34家族水平较高的SC-M1和AZ521胃癌细胞中，敲低miR-34家族通过上调YY1促进了肿瘤发生。miR-34家族还通过YY1影响肿瘤球的超微结构，抑制SC-M1细胞的异种移植肿瘤生长以及肺转移。患者胃癌组织中miR-34a和miR-34c的表达低于正常组织。综上所述，这些结果表明miR-34家族-YY1轴在胃癌发生的控制中起重要作用。
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