Novel functions of circRNA found in small cell lung cancer

Recently, researchers led by Prof. LIN Wenchu from High Magnetic Field Laboratory, Hefei Institutes of Physical Science (HFIPS) of Chinese Academy of Sciences (CAS) proposed a mechanism by which circular RNA (circRNA) can promote the progression of small cell lung cancer (SCLC) in vitro and in vivo.

This work was published on Molecular Cancer.

Small cell lung cancer was a recalcitrant cancer with limited treatment options. The overall 5-year relative survival rate for SCLC was less than 7%. Covalently closed circular RNAs (circRNAs) were single-stranded endogenous RNA molecules with loop structures that played critical roles in cancer initiation, progression, and metastasis, yet the biological functions of circRNAs in SCLC were still elusive.

In this research, the circRNA-circVAPA, which was derived from exons 2-4 of the vesicle-associated membrane protein-associated protein A (VAPA) gene, exhibited higher expression levels in SCLC than the controls.

"We found that CircVAPA exerted a cancer-promoting effect on small cell lung cancer by modulating the miR-377-3p and miR-494-3p/IGF1R/AKT axis," said Prof.Lin. "this  expanded our knowledge about circRNAs in SCLC."

Furthermore, circVAPA depletion markedly enhanced the inhibitory effects of BMS-536924, an IGF1R kinase inhibitor in cellular and xenograft mouse models, providing a novel therapeutic strategy for treating SCLC.