A group of glycolysis-related aberrant miRNAs of radioiodine-refractory differentiated thyroid cancer

Background: Most of differentiated thyroid cancer (DTC) has good prognosis even with radioiodine-avid (RAIA) distant metastases. However, 30-40% of patients with distant metastases develop losing the ability to accumulate radioiodine, and hence are refractory to RAI(RAIR), the median of overall survival is about 3 years. The loss of differentiation features is always accompanied with glycolysis enhanced, demonstrating as positive ¹⁸F-FDG PET/CT with negative ¹³¹I whole body scan. This study focuses the role of miRNA involved in the glycolysis change of the RAIR DTC.

Methods: miRCURY^TM LNA Array (v.18.0, Exiqon) was used to identify a subset of differentially expressed miRNAs between RAIA and RAIR PTC with lung metastases. Aberrant glycolysis-related miRNAs were validated their regulation gene and their biological effect on BCPAP cell line.

Results: The miRNA array identified eight miRNAs upregulation and 25 miRNAs downregulation in four RAIR compared with three RAIA PTC samples (1.5-fold higher or lower, P<0.05). Among downregulation miRNAs, there were 3 miRNAs related with glycolysis. They are miR-22-3p, miR-30d-5p and miR-125a-5p, which demonstrated as inhibiting glucose transporter 1 (GLUT-1), lactate dehydrogenase-A (LDHA) and CD147, the key molecules in glycolysis, respectively. The inhibition of miR-22-3p promoted BCPAP cell proliferation, without effect on migration and invasion,while inhibition of miR-30d-5p and miR-125a-5p markedly promoted BCPAP cell growth, migration and invasion, overexpression miR-30d-5p show stronger inhibition capabilities on invasion than miR-125a-5p.

Conclusions: RAIR DTC has a group of reduced expression miRNA related glycolysis, involved in glucose transportation, lactate produce and transportation, then promote RAIR show more aggressive biological behaviors.