Yin Yang 1 is a target of microRNA-34 family and contributes to gastric carcinogenesis

An-Ming Wang; Tzu-Ting Huang; Kai-Wen Hsu; Kuo-Hung Huang; Wen-Liang Fang; Muh-Hwa Yang; Su-Shun Lo; Chin-Wen Chi; Jing-Jer Lin; Tien-Shun Yeh

doi:10.18632/oncotarget.2073

Yin Yang 1 is a target of microRNA-34 family and contributes to gastric carcinogenesis

Oncotarget. 2014 Jul 15;5(13):5002-16. doi: 10.18632/oncotarget.2073.

Authors

An-Ming Wang¹, Tzu-Ting Huang², Kai-Wen Hsu³, Kuo-Hung Huang⁴, Wen-Liang Fang⁴, Muh-Hwa Yang⁵, Su-Shun Lo⁶, Chin-Wen Chi⁷, Jing-Jer Lin⁸, Tien-Shun Yeh⁹

Affiliations

¹ 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.
² 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.
³ Department of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei , Taiwan. These authors contributed equally to this work.
⁴ Department of Surgery, Taipei Veterans General Hospital, Taipei , Taiwan. Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei , Taiwan. These authors contributed equally to this work.
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. Department of Surgery, National Yang-Ming University Hospital, Yi-Lan, Taiwan.
⁷ Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei , Taiwan. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei , Taiwan.
⁸ Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei , Taiwan. Institute of Biochemistry and Molecular Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
⁹ Department of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei , Taiwan. Genome Research Center, National Yang-Ming University, Taipei , Taiwan. Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3' Untranslated Regions / genetics
Animals
Blotting, Western
Cell Line, Tumor
Cell Movement / genetics
Cell Proliferation
Cell Survival / genetics
Gene Expression Regulation, Neoplastic*
Humans
Mice, Inbred BALB C
Mice, Nude
MicroRNAs / genetics*
RNA Interference
Reverse Transcriptase Polymerase Chain Reaction
Stomach Neoplasms / genetics*
Stomach Neoplasms / metabolism
Tumor Burden / genetics
Xenograft Model Antitumor Assays / methods
YY1 Transcription Factor / genetics*
YY1 Transcription Factor / metabolism

Substances

3' Untranslated Regions
MIRN34 microRNA, human
MicroRNAs
YY1 Transcription Factor
YY1 protein, human