期刊
ONCOTARGET
卷 5, 期 13, 页码 5002-5016出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.2073
关键词
YY1; miR-34 family; gastric cancer; carcinogenesis; pluripotency
资金
- Electron Microscopy Facility in National Yang-Ming University
- National Science Council [NSC 101-2320-B-010-067-MY3]
- Ministry of Education, Aim for the Top University Plan [103AC-T403]
- Center of Excellence for Cancer Research at Taipei Veterans General Hospital [DOH102-TD-111-007, MOHW103-TD-B-111-02]
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 multifunctional 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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