Professor Yong Peng's team from the State Key Laboratory of Biotherapy(SKLB) at West China Hospital recently published a paper titled "A Circular RNA Activated by TGFβ Promotes Tumor Metastasis Through Enhancing IGF2BP3-Mediated PDPN mRNA Stability", and discovered that the circular RNA activated by TGFβ (circITGB6) promotes epithelial mesenchymal transition and tumor metastasis through a novel mechanism, revealing the potential of circular RNA as a new target for intervening in tumor metastasis.
Tumor metastasis is the primary cause of mortality, and there is no effective treatment strategy.During the early stage of metastasis, a subset of cancer cells undergoes epithelial-mesenchymal transition (EMT) by which they acquire mesenchymal features and were thus equipped with the ability to disseminate from their primary sites and travel to distant organs. Once cancer cells escape from the primary sites, the cancer would develop an incurable disease as the metastatic cancer cells are hardly eradicated.Yong Peng's team has recently demonstrated the important role of circular RNA in tumor metastasis (PNAS, 2023120: e2215132120), suggesting an intrinsic connection between abnormal expression of circular RNA and the EMT process.
"---, the involvement of circRNAs in this process is still obscure. Here, we identify a TGFβ-induced circRNA called circITGB6 as an indispensable factor during the TGFβ-mediated EMT process. circITGB6 is significantly upregulated in metastatic cancer samples and its higher abundance is closely correlated to worse prognosis of colorectal cancer (CRC) patients. Through gain- and loss-of-function assays, circITGB6 is found to potently promote EMT process and tumor metastasis in various models in vitro and in vivo. Mechanistically, circITGB6 enhances the mRNA stability of PDPN, an EMT-promoting gene, by directly interacting with IGF2BP3. Notably, interfering circITGB6 with PEI-coated specific siRNA effectively represses liver metastasis. Therefore, our study reveals the function of a TGFβ-regulated circRNA in tumor metastasis and suggests that targeting circITGB6 is a promising strategy for cancer therapy." (Abstract)
Dr. Ke Li and Dr. Jiawei Guo from the SKLB are co first authors, and Yong Peng is the corresponding author.This work was supported by the National Key R&D Program of China (2022YFA1303200), National Natural Science Foundation of China (82002570 to K.L. and 82102982 to J.G.), and so forth.
https://www.nature.com/articles/s41467-023-42571-1
