miR-590-5p mediates mitochondrial respiration, proliferation, and apoptosis in thyroid carcinoma cells via fibroblast growth factor receptor substrate 2.

OBJECTIVE

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.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSION

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.