Down-Regulated miR-125a-5p Promotes the Reprogramming of Glucose Metabolism and Cell Malignancy by Increasing Levels of CD147 in Thyroid Cancer

Abstract

Background:

CD147 contributes to increased aerobic glycolysis through which it promotes tumor growth. Accumulating evidence suggests that CD147 exerts a variety of functions in thyroid cancer (TC) progression but the molecular mechanisms and therapeutic value of CD147 remain unclear.

Methods:

CD147 levels in TC tissues were analyzed to assess its relationship with prognosis and disease progression. A microRNA (miRNA) microarray and bioinformatics approach were used to identify microRNA regulators of CD147 through measurement of the expression and functions of these miRNAs in TC tissues and cell lines. Precursor miRNA-transfected cells were used to assess regulation of CD147 by miRNA. The effect of miRNA on TC cells via inhibition of glycolysis through CD147 targeting was also evaluated.

Results:

We found that miR-125a-5p regulates CD147 and is negatively correlated with its expression and function. Moreover, CD147 knockdown or increased miR-125a-5p expression significantly reduced the viability, migration, and invasion of TC cells. Our mechanistic studies demonstrate that, through directly repressing the expression of the CD147 protein, miR-125a-5p suppresses aerobic glycolysis and lactate production and subsequently reduces TC cell viability, migration, and invasion, thereby exerting tumor suppressor functions.

Conclusions:

The novel connection identified between miR-125a-5p and CD147 suggests a new diagnostic and prognostic role for miR-125a-5p and that CD147 inhibition may be a candidate therapeutic target in the therapy of for TC.