Circular RNA hsa_circ_0002938 (circCRIM1) promotes the progression of esophageal squamous cell carcinoma by upregulating transcription factor 12

Xiao-Peng Li, Yun-Long Jia, Yu-Qing Duan, Yan Zhao, Xiao-Lei Yin, Shu-Man Zhen, Yi Zhang,  Li-Hua Liu

Abstract:

Growing evidence has indicated that circular RNAs (circRNAs) play crucial roles in the tumorigenesis and progression of diverse malignancies. However, the majority of circRNAs involved in esophageal squamous cell carcinoma (ESCC) remain undefined and the exact functions and underlying mechanisms of circRNAs in ESCC still need further exploration. In this study, we identified a novel onco-circRNA hsa_circ_0002938, derived from the exons of cysteine-rich transmembrane BMP regulator 1 (CRIM1) pre-mRNA, referred to as circCRIM1. We found that the expression of circCRIM1 was higher in ESCC tissues, compared to para-carcinoma tissues. Increased expression of circCRIM1 was positively correlated with clinical parameters of ESCC patients including tumor-node-metastasis (TNM) stage, tumor invasion range, and lymph node metastasis. Functionally, the results from the experiments in vitro showed that the knockdown of circCRIM1 suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in ESCC cells. By conducting bioinformatics algorithms analyses and microRNA (miRNA) rescue experiments, we found that circCRIM1 could act as a competing endogenous RNA (ceRNA) to sponge miR-342-3p in ESCC cells, and thereby upregulated the expression of transcription factor 12 (TCF12), a key regulator promoting the EMT process. Taken together, circCRIM1 facilitates the progression of ESCC by sponging miR-342-3p to regulate TCF12 and promote EMT, and the circCRIM1/miR-342-3p/TCF12 axis may be regarded as a potential predictive biomarker and therapeutic target for treating ESCC.