Li Xiao-Peng, Jia Yun-Long, Duan Yu-Qing, Zhao Yan, Yin Xiao-Lei, Zhen Shu-Man, Zhang Yi, Liu Li-Hua
Department of Tumor Immunotherapy, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Medical Record Room, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Neoplasma. 2023 Feb;70(1):145-157. doi: 10.4149/neo_2023_220823N857.
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.
越来越多的证据表明，环状RNA（circRNAs）在多种恶性肿瘤的发生和发展中起着关键作用。然而，大多数参与食管鳞状细胞癌（ESCC）的circRNAs仍未明确，其在ESCC中的确切功能和潜在机制仍需进一步探索。在本研究中，我们鉴定了一种新的致癌circRNA hsa_circ_0002938，它来源于富含半胱氨酸的跨膜BMP调节因子1（CRIM1）前体mRNA的外显子，称为circCRIM1。我们发现，与癌旁组织相比，circCRIM1在ESCC组织中的表达更高。circCRIM1表达的增加与ESCC患者的临床参数呈正相关，包括肿瘤-淋巴结-转移（TNM）分期、肿瘤侵袭范围和淋巴结转移。在功能上，体外实验结果表明，敲低circCRIM1可抑制ESCC细胞的增殖、迁移、侵袭和上皮-间质转化（EMT）。通过进行生物信息学算法分析和微小RNA（miRNA）拯救实验，我们发现circCRIM1可以作为一种竞争性内源性RNA（ceRNA），在ESCC细胞中吸附miR-342-3p，从而上调转录因子12（TCF12）的表达，TCF12是促进EMT过程的关键调节因子。综上所述，circCRIM1通过吸附miR-342-3p来调节TCF12并促进EMT，从而促进ESCC的进展，circCRIM1/miR-342-3p/TCF12轴可能被视为治疗ESCC的潜在预测生物标志物和治疗靶点。
