Circular RNA circ-TNPO3 suppresses metastasis of GC by acting as a protein decoy for IGF2BP3 to regulate the expression of MYC and SNAIL

• Published in: Molecular therapy. Nucleic acids Vol. 26; pp. 649 - 664
• Main Authors: Yu, Ting, Ran, Lingyu, Zhao, Hongwen, Yin, Pin, Li, Wei, Lin, Jie, Mao, Hui, Cai, Dongping, Ma, Qiang, Pan, Xiaojuan, Wang, Xiaolin, Wu, Jingjing, Zeng, Hao, Zhang, Weijun, Lu, Dongshui, Luo, Ping, Zou, Quanming, Xiao, Bin
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 03.12.2021; American Society of Gene & Cell Therapy; Elsevier
• Subjects: circ-TNPO3; gastric cancer; IGF2BP3; MYC; Original; protein decoy; SNAIL; circ-TNPO3; IGF2BP3; gastric cancer; protein decoy; MYC; SNAIL
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1016/j.omtn.2021.08.029

Gastric cancer (GC) continues to be the most common gastrointestinal malignancy in China, and tumor metastases are a major reason for poor prognosis. Circular RNAs (circRNAs) are an intriguing type of noncoding RNAs with important regulatory roles. However, the roles of circRNAs in GC metastasis have not been fully elucidated. Here, we reported that circ-transportin 3 (TNPO3) was significantly downregulated in 103 pairs of GC tissues compared with matched noncancerous tissues. The level of circ-TNPO3 expression correlated with differentiation of GC, and plasma circ-TNPO3 could serve as a potential diagnostic biomarker. Functionally, circ-TNPO3 inhibited proliferation and migration of GC in vitro and in vivo. We further verified that circ-TNPO3 competitively interacted with insulin-like growth factor 2 binding protein 3 (IGF2BP3) protein; thus, the role of IGF2BP3 in stabilizing MYC mRNA was weakened, which inhibited the expression of MYC and its target SNAIL. Taken together, circ-TNPO3 acts as a protein decoy for IGF2BP3 to regulate the MYC-SNAIL axis, thereby suppressing the proliferation and metastasis of GC. Therefore, circ-TNPO3 has the potential to serve as a therapeutic target for GC. [Display omitted] circ-TNPO3 acts as a protein decoy for IGF2BP3 to inhibit the expression of MYC and SNAIL. In GC, the downregulated circ-TNPO3 weakens its interaction with IGF2BP3 and promotes the expression of MYC and its target gene SNAIL, thereby resulting in GC metastasis.