Related Experiment Videos
miR-135a inhibits tumor metastasis and angiogenesis by targeting FAK pathway
Zhenguo Cheng1, Funan Liu2, Hongyan Zhang1
1Department 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.
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.
Insights
MicroRNA-135a (miR-135a) is downregulated in gastric cancer, inhibiting tumor growth and metastasis. Restoring miR-135a shows therapeutic potential by targeting the focal adhesion kinase (FAK) pathway.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Tumor metastasis is a primary driver of gastric cancer recurrence and mortality.
- MicroRNAs (miRNAs) play crucial roles in cancer development and progression.
- The specific role of miR-135a in gastric cancer metastasis requires further elucidation.
Purpose of the Study:
- To investigate the expression profile of miR-135a in gastric cancer.
- To determine the functional role of miR-135a in gastric cancer progression and metastasis.
- To uncover the regulatory mechanisms involving miR-135a in gastric cancer.
Main Methods:
- MicroRNA array analysis to compare miR-135a expression in metastatic vs. parental gastric cancer cell lines.
- Analysis of miR-135a expression in human gastric cancer tissues and cell lines.
- Functional assays (in vitro and in vivo) to assess the impact of miR-135a restoration on tumor growth, migration, invasion, and angiogenesis.
- Bioinformatics and molecular experiments to identify downstream targets and regulatory pathways, including the focal adhesion kinase (FAK) and p53 pathways.
Main Results:
- miR-135a expression is significantly decreased in metastatic gastric cancer cell lines and human gastric cancer tissues.
- Lower miR-135a expression correlates with advanced TNM stage and poorer patient survival.
- Restoration of miR-135a inhibits gastric cancer cell growth, migration, invasion, and angiogenesis by targeting the FAK pathway.
- miR-135a is identified as a novel downstream target of the tumor suppressor p53.
- Inhibition of FAK enhances miR-135a expression via p53 induction.
Conclusions:
- miR-135a acts as a tumor suppressor in gastric cancer, with its downregulation promoting metastasis.
- The miR-135a/FAK pathway represents a potential therapeutic target for gastric cancer.
- A novel regulatory feedback loop involving p53, miR-135a, and FAK in gastric cancer is uncovered.