The Role of Yin Yang 1 in Gastric Carcinogenesis

• Main Authors: An-Ming Wang, 王安民
• Other Authors: Jing-Jer Lin
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/23392864820138891272

博士 === 國立陽明大學 === 生物藥學研究所 === 102 === Gastric cancer is one of the most common and the second leading cause of cancer-related death worldwide. Transcription factor Yin Yang 1 (YY1) is a multi-functional protein and plays either oncogenic or tumor-suppressive roles in tumor development and progression. Herein, we investigated the role of YY1 in tumorigenesis of gastric cancer cells. Based on the results of TCGA analysis, YY1 expression was higher in gastric cancer tissues. Results showed that the forced expression of YY1 in SC-M1 gastric cancer cells contributes to gastric carcinogenesis including growth, viability, and abilities of colony formation, migration, invasion, and tumorsphere formation. The expression of pluripotent genes CD44, Oct4, SOX-2, and Nanog were also up-regulated by YY1 in SC-M1 cells. Whereas, knockdown of endogenous YY1 suppresses tumorigenesis of SC-M1 cells. In addition, the YY1 mRNA 3’-untranslated region (3’-UTR) was the target of microRNA-34 (miR-34) family consisting of miR-34a, miR-34b, and miR-34c. The ectopic expression of miR-34 family down-regulates YY1 levels in gastric cancer cells. The endogenous YY1 expression is negatively correlated with miR-34b and miR-34c levels in several gastric cancer cell lines. Besides SC-M1 cells, the exogenous miR-34 family suppresses gastric carcinogenesis through down-regulation of YY1 in NUGC-3 gastric cancer cells which expressed low level of miR-34 family. Alternatively, knockdown of endogenous miR-34 family promotes gastric carcinogenesis through up-regulation of YY1 in SC-M1 and AZ521 gastric cancer cells with higher levels of miR-34 family. The miR-34 family-YY1 axis also affected tumorsphere ultra-structure and inhibited xenografted tumor growth as well as lung metastasis of SC-M1 cells and participates in negative-feedback loop of YY1 and miR-206. Expressions of miR-34a, miR-34c, and miR-206 in gastric cancer tissues of patients were lower than those in normal tissues. Taken together, these results suggest that miR-34 family-YY1 axis exerts its function through modulating EMT-related as well as pluripotent genes and plays an important role in the control of gastric carcinogenesis.