ThermomiR-377-3p-induced suppression of Cirbp expression is required for effective elimination of cancer cells and cancer stem-like cells by hyperthermia

作者：Taoyan Lin, Jun-Shuang Jia, Weiren Luo, Xiaolin Lin, Shengjun Xiao, Jie Yang, Jia‐Wei Xia, Chen Zhou, Zhihao Zhou, Shujun Lin, Qi-Wen Li, Zhi-Zhi Yang, Lei Ye, Wenqing Yang, Hong-Fen Shen, Shihao Huang, Shengchun Wang, Lin-Bei Chen, Yulin Yang, Shu-Wen Xue, Yonglong Li, Guanqi Dai, Ying Zhou, Ying-Chun Li, Fang Wei, Xiaoxiang Rong, Xiaojun Luo, Bingxia Zhao, Wenhua Huang, Dong Xiao, Yan Sun · 发表于：Journal of Experimental & Clinical Cancer Research · 年份：2024 · DOI：10.1186/s13046-024-02983-3 · 被引用次数：14 · 研究领域：Thermal Regulation in Medicine、Ultrasound and Hyperthermia Applications、Heat shock proteins research

BACKGROUND: In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold‑inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). METHODS: CCK-8 assay, colony formation assay, tumor sphere formation assay, qRT-PCR, Western blot were employed to examine the effects of hyperthermia (HT), HT + oridonin(Ori) or HT + radiotherapy (RT) on the proliferation and stemness of NPC cells. RNA sequencing was applied to gain differentially expressed genes upon hyperthermia. Gain-of-function and loss-of-function experiments were used to evaluate the effects of RNAi-mediated Cirbp silencing or Cirbp overexpression on the sensitivity or resistance of NPC cells and cancer stem-like cells to hyperthermia by CCK-8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay, and in subcutaneous xenograft animal model. miRNA transient transfection and luciferase reporter assay were used to demonstrate that Cirbp is a direct target of miR-377-3p. The phosphorylation levels of key members in ATM-Chk2 and ATR-Chk1 pathways were detected by Western blot. RESULTS: Our results firstly revealed that hyperthermia significantly attenuated the stemness of NPC cells, while combination treatment of hyperthermia ...