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, Tian-Shun Tsai

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5002-5016
Number of pages15
JournalOncotarget
Volume5
Issue number13
Publication statusPublished - 2014

Keywords

  • Carcinogenesis
  • Gastric cancer
  • miR-34 family
  • Pluripotency
  • YY1

ASJC Scopus subject areas

  • Oncology
  • Medicine(all)

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