Yin Yang 1 is a target of microRNA-34 family and contributes to gastric carcinogenesis
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An-Ming Wang1,2, Tzu-Ting Huang2,3,*, Kai-Wen Hsu2,*, Kuo-Hung Huang4,5,*, Wen-Liang Fang4,5,*, Muh-Hwa Yang5, Su-Shun Lo6,7, Chin-Wen Chi3,8, Jing-Jer Lin1,9 and Tien-Shun Yeh2,10,11
1 Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei , Taiwan
2 Department of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei , Taiwan
3 Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei , Taiwan
4 Department of Surgery, Taipei Veterans General Hospital, Taipei , Taiwan
5 Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei , Taiwan
6 Department of Medicine, School of Medicine, National Yang-Ming University, Taipei , Taiwan
7 Department of Surgery, National Yang-Ming University Hospital, Yi-Lan, Taiwan
8 Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei , Taiwan
9 Institute of Biochemistry and Molecular Biology, National Taiwan University College of Medicine, Taipei, Taiwan
10 Genome Research Center, National Yang-Ming University, Taipei , Taiwan
11 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
* These authors contributed equally to this work.
Tien-Shun Yeh, email:
Jing-Jer Lin, email:
Keywords: YY1/miR-34 family/gastric cancer/carcinogenesis/pluripotency
Received: March 20, 2014 Accepted: June 6, 2014 Published: June 7, 2014
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.
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