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Suppressing the Spread of Gastric Cancer Cells With Circular RNA

Researchers from the Chinese Academy of Sciences proposed a mechanism involving circular RNA and cancer metastasis.

Circular RNAs are a class of natural covalent closed single-stranded RNA molecules that have surfaced as important regulators of human cancers, however, not much is known of its role in gastric cancers. Although the frequency of gastric cancers has decreased globally, it still ranks as the fifth most common cancer in the world. While the prevalence of gastric cancer varies from country to country, its incidence is reported to be high in East Asian countries. Limiting the metastatic spread of gastric cancer is key to improving its prognosis.

In a study led by Professor Lin Wenchu of the Hefei Institutes of Physical Science, in collaboration with Professor Shan Ge and Associate Professor Hu Shanshan from the University of Science and Technology of China, the team presented a mechanism by which circular RNA can repress gastric cancer metastasis. This circular RNA, called circURI1, interacts with heterogeneous nuclear ribonucleoprotein M (hnRNPM) and sequesters it to regulate alternative splicing of genes that are involved in cell migration, thereby repressing gastric cancer metastasis.

In the study, the research team carried out gastric cancer circular RNA profiling and classified circURI1 as having a higher expression in gastric cancer than the corresponding non-tumour tissues. They then conducted loss-of-function and gain-of-function studies, which revealed that circURI1 suppressed cell migration and invasion in vitro and gastric cancer metastasis in vivo.

From these results, the study presents the first reported association of circular RNA, alternative splicing, and metastasis, broadening the present knowledge regarding the molecular mechanism of circular RNA-mediated cancer metastasis through alternative splicing regulation.

Source: Wang et al. (2021). CircURI1 interacts with hnRNPM to inhibit metastasis by modulating alternative splicing in gastric cancer. Proceedings of the National Academy of Sciences, 118(33).