miR-135a inhibits tumor metastasis and angiogenesis by targeting FAK pathway

// Zhenguo Cheng 1 , Funan Liu 2 , Hongyan Zhang 1 , Xiaodong Li 1 , Yanshu Li 1 , Jiabin Li 1 , Furong Liu 1 , Yu Cao 1 , Liu Cao 1 , Feng Li 1 1 Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China 2 Department of Surgical Oncology, The first Hospital of China Medical University, Shenyang 110001, China Correspondence to: Feng Li, email: fli@mail.cmu.edu.cn Keywords: gastric cancer, metastasis, miR-135a, FAK, p53 Received: September 27, 2016 Accepted: March 01, 2017 Published: March 10, 2017 ABSTRACT Tumor metastasis has been the major cause of recurrence and death in patients with gastric cancer. Here, we find miR-135a has a decreased expression in the metastatic cell lines compared with its parental cell lines by analyzing microRNA array. Further results show that miR-135a is downregulated in the majority of human gastric cancer tissues and cell lines. Decreased expression of miR-135a is associated with TNM stage and poor survival. Besides, regaining miR-135a in gastric cancer cells obviously inhibits tumor growth, migration, invasion and angiogenesis by targeting focal adhesion kinase (FAK) pathway. Bioinformatics analysis and molecular experiments further prove that miR-135a is a novel downstream gene of tumor suppressor p53. Blocking FAK with its inhibitor can also enhance miR-135a expression through inducing p53. In summary, this study reveals the expression and function of miR-135a in gastric cancer and uncovers a novel regulatory mechanism of miR-135a.