Li Lin, Lei Kai, Lyu Yingcheng, Tan Binghua, Liang Ruihao, Wu Duoguang, Wang Kefeng, Wang Wenjian, Lin Huayue, Wang Minghui
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University Guangzhou, Guangdong, China.
Department of Thoracic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University Guangzhou, Guangdong, China.
Am J Cancer Res. 2022 May 15;12(5):2012-2031. eCollection 2022.
Circular RNAs (circRNAs) have been reported to play crucial roles in the progression of various cancers, including esophageal squamous cell carcinoma (ESCC). However, the function of circRNAs in ESCC stemness has not been reported. This study aimed to identify novel circRNAs that regulate ESCC stemness and explore their internal mechanisms in ESCC. We found that hsa_circ_0001741 was upregulated in ESCC tissues and was positively related to lymphatic metastasis, higher TNM stage, and poor prognosis. Functionally, hsa_circ_0001741 promoted ESCC cell stemness, invasion, and migration . Mechanistically, analysis of the relationship between hsa_circ_0001741 and tumor suppressor miR-491-5p revealed that hsa_circ_0001741 functioned as a miR-491-5p sponge. Specifically, hsa_circ_0001741 bound to miR-491-5p to prevent the microRNA from binding to the 3'-UTR of NOTCH3 mRNA and suppressing NOTCH3 expression. Moreover, the ablation of hsa_circ_0001741 significantly inhibited the tumorigenicity . In conclusion, hsa_circ_0001741 promotes ESCC stemness, invasion, and migration by sponging tumor suppressor miR-491-5p to upregulate NOTCH3 expression. Our findings identify a novel therapeutic target for ESCC patients and the expression level of hsa_circ_0001741 has the potential to serve as a prognostic biomarker for ESCC.
据报道,环状RNA(circRNAs)在包括食管鳞状细胞癌(ESCC)在内的各种癌症进展中发挥关键作用。然而,circRNAs在ESCC干性中的功能尚未见报道。本研究旨在鉴定调控ESCC干性的新型circRNAs,并探索其在ESCC中的内在机制。我们发现hsa_circ_0001741在ESCC组织中上调,且与淋巴转移、较高的TNM分期和不良预后呈正相关。在功能上,hsa_circ_0001741促进ESCC细胞的干性、侵袭和迁移。机制上,对hsa_circ_0001741与肿瘤抑制因子miR-491-5p之间关系的分析表明,hsa_circ_0001741充当miR-491-5p的海绵。具体而言,hsa_circ_0001741与miR-491-5p结合,以防止该微小RNA与NOTCH3 mRNA的3'-UTR结合并抑制NOTCH3表达。此外,hsa_circ_0001741的缺失显著抑制了肿瘤发生。总之,hsa_circ_0001741通过充当肿瘤抑制因子miR-491-5p的海绵来上调NOTCH3表达,从而促进ESCC的干性、侵袭和迁移。我们的研究结果为ESCC患者确定了一个新的治疗靶点,并且hsa_circ_0001741的表达水平有可能作为ESCC的预后生物标志物。