Wang Penghui, Hou Xiaoli, Sun Wei, Chen Jiajie, Cao Yasen, Cheng Hong
Yangzhou University Medical College Yangzhou China Yangzhou University Medical College, Yangzhou, China.
Affiliated Hospital of Yangzhou University Department of Clinical Laboratory Yangzhou China Department of Clinical Laboratory, Affiliated Hospital of Yangzhou University, Yangzhou, China.
Arch Endocrinol Metab. 2025 Aug 20;69(4):e240410. doi: 10.20945/2359-4292-2024-0410.
Thyroid carcinoma (TC) is the most common cancer of the endocrine system. Dysregulation of microRNA-590-5p (miR-590-5p) has been associated with various malignancies. Targeting mitochondrial respiration is beneficial in treating TC. This study aims to evaluate the role of miR-590-5p in the proliferation and apoptosis of TC cells via mediating mitochondrial respiration.
Reverse transcription quantitative polymerase chain reaction (qRT-PCR) was used to analyze differential expression of miR-590-5p in TC and para-cancerous tissues, normal thyrocytes, and TC cell lines. TC cells were transfected with agomiRNA negative control (agomiR-NC) or agomiRNA-590-5p (agomiR-590-5p). Cell counting kit 8 (CCK-8) assays, JC-1 staining, reactive oxygen species (ROS) measurements, and flow cytometry were used to detect cell proliferation, mitochondrial membrane potential (MMP), ROS levels, and apoptosis, respectively. The targeting relationship between miR-590-5p and fibroblast growth factor receptor substrate 2 (FRS2) was verified using dual-luciferase reporter assay. The role of miR-590-5p in tumor growth was analyzed in mouse xenograft tumors.
miR-590-5p was expressed at low levels in TC tissues and cells relative to normal tissues. Overexpression of miR-590-5p reduced TC cell proliferation, enhanced apoptosis, and inhibited mitochondrial respiration. miR-590-5p suppressed FRS2 transcription in TC cells. Overexpression of FRS2 reversed the effects of miR-590-5p overexpression, limiting mitochondrial respiration and proliferation, and promoting apoptosis. In vivo, overexpression of miR-590-5p suppressed xenograft tumor growth in mice by reducing the transcription of FRS2.
miR-590-5p was poorly expressed in TC. Overexpression of miR-590-5p limited TC cell proliferation and promoted apoptosis by reducing mitochondrial respiration via decreased transcription of FRS2.
甲状腺癌（TC）是内分泌系统最常见的癌症。微小RNA-590-5p（miR-590-5p）失调与多种恶性肿瘤有关。靶向线粒体呼吸对治疗TC有益。本研究旨在评估miR-590-5p通过介导线粒体呼吸在TC细胞增殖和凋亡中的作用。
采用逆转录定量聚合酶链反应（qRT-PCR）分析miR-590-5p在TC及癌旁组织、正常甲状腺细胞和TC细胞系中的差异表达。用agomiRNA阴性对照（agomiR-NC）或agomiRNA-590-5p（agomiR-590-5p）转染TC细胞。分别用细胞计数试剂盒8（CCK-8）检测、JC-1染色、活性氧（ROS）检测和流式细胞术检测细胞增殖、线粒体膜电位（MMP）、ROS水平和凋亡。采用双荧光素酶报告基因检测法验证miR-590-5p与成纤维细胞生长因子受体底物2（FRS2）的靶向关系。在小鼠异种移植瘤中分析miR-590-5p在肿瘤生长中的作用。
与正常组织相比，miR-590-5p在TC组织和细胞中低表达。miR-590-5p过表达可降低TC细胞增殖，增强凋亡，并抑制线粒体呼吸。miR-590-5p抑制TC细胞中FRS2的转录。FRS2过表达逆转了miR-590-5p过表达的作用，限制了线粒体呼吸和增殖，并促进了凋亡。在体内，miR-590-5p过表达通过降低FRS2的转录抑制小鼠异种移植瘤的生长。
miR-590-5p在TC中表达不足。miR-590-5p过表达通过降低FRS2转录减少线粒体呼吸，从而限制TC细胞增殖并促进凋亡。
