Researchers from the Chinese Academy of Sciences (CAS) recently proposed a mechanism by which circular RNA (circRNA) can suppress the metastasis of gastric cancer cells. 

This circRNA, called circURI1, exerts an anti-metastatic effect by sequestering heterogeneous nuclear ribonucleoprotein M (hnRNPM) in order to modulate alternative splicing in gastric cancer. It is the first reported association between circRNA and alternative splicing. This work was published in PNAS online. 

Gastric cancer is the fifth most common malignant tumor and the third leading cause of cancer death worldwide, largely due to its metastatic spread in patients. CircRNAs are a class of natural covalent closed single-stranded RNA molecules that have emerged as key regulators of human cancers, yet their modes of action in gastric cancer have remained obscure. 

Led by Prof. LIN Wenchu of the Hefei Institutes of Physical Science (HFIPS), in collaboration with Prof. SHAN Ge and Associate Prof. HU Shanshan from the University of Science and Technology of China, the researchers performed gastric cancer circRNA profiling and identified circURI1 as having higher expression in gastric cancer compared to corresponding non-tumor tissues. Loss-of-function and gain-of-function studies revealed that circURI1 repressed cell migration and invasion in vitro and gastric cancer metastasis in vivo. 

Mechanistically, circURI1 acts directly interacts with hnRNPM in a sequence-dependent manner to modulate alternative splicing of a subset of genes related to cell migration, thus suppressing gastric cancer metastasis. 

This study provides a new perspective on the molecular basis of cancer metastasis by highlighting the activity of circRNAs, and suggests that circURI1 may play a potential role in the diagnosis and treatment of gastric cancer. 

This study was supported by the National Natural Science Foundation of China, the National Key Research and Development Program of China, the Science and Technology Major Project Program of Anhui Province, and the Strategic Priority Research Program, "Biological Basis of Aging and Therapeutic Strategies" of CAS. 

Identification of circURI1 (Image by WANG Xiaolin) 

CircURI1 suppresses cell invasion and gastric cancer metastasis (Image by WANG Xiaolin) 

The functional mechanism of circURI1 in GC metastasis (Image by WANG Xiaolin)