CircMALAT1 promotes cancer stem‐like properties and chemoresistance via regulating Musashi‐2/c‐Myc axis in esophageal squamous cell carcinoma
Zitong Zhao,
Yingni Deng,
Jing Han,
Liying Ma,
Yumeng Zhu,
Hua Zhang,
Zhixu He,
Yongmei Song
Affiliations
Zitong Zhao
Key Laboratory of Cancer and Microbiome State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
Yingni Deng
Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine Zunyi Medical University Zunyi China
Jing Han
Department of Oncology The Fourth Hospital of Hebei Medical University Shijiazhuang Hebei China
Liying Ma
Key Laboratory of Cancer and Microbiome State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
Yumeng Zhu
Key Laboratory of Cancer and Microbiome State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
Hua Zhang
School of Continuing Education Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China
Zhixu He
Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine Zunyi Medical University Zunyi China
Yongmei Song
Key Laboratory of Cancer and Microbiome State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
Abstract The primary challenge in treating esophageal squamous cell carcinoma (ESCC) is resistance to chemotherapy. Cancer stem cell (CSC) is the root cause of tumor drug resistance. Therefore, targeting CSCs has been considered promising therapeutic strategy for tumor treatment. Here, we report that circMALAT1 was significantly upregulated in ESCC CSC‐like cells and primary tumors from ESCC patients. Clinically, there was a positive correlation between circMALAT1 expression and ESCC stage and lymph node metastasis, as well as poor prognosis for ESCC patients. In vitro and in vivo functional studies revealed that circMALAT1 promoted CSC‐like cells expansion, tumor growth, lung metastasis and drug resistance of ESCC. Mechanistically, circMALAT1 directly interacted with CSC‐functional protein Musashi RNA Binding Protein 2 (MSI2). CircMALAT1 inhibited MSI2 ubiquitination by preventing it from interacting with β‐transducin repeat containing protein (BTRC) E3 ubiquitin ligase. Also, circMALAT1 knockdown inhibited the expression of MSI2‐regulating CSC‐markers c‐Myc in ESCC. Collectively, circMALAT1 modulated the ubiquitination and degradation of the MSI2 protein signaling with ESCC CSCs and accelerated malignant progression of ESCC. CircMALAT1 has the potential to serve as a biomarker for drug resistance and as a target for therapy in CSCs within ESCC.
