MiR-505 suppressed the growth of hepatocellular carcinoma cells via targeting IGF-1R.

Liang Ren,Yang Wang,Yongshan Yao,Shengqiang Wang

doi:10.1042/bsr20182442

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers globally. An increasing body of evidence has demonstrated the critical function of microRNAs (miRNAs) in the initiation and progression of human cancers. Here, we showed that miR-505 was down-regulated in HCC tissues and cell lines. Reduced expression of miR-505 was significantly correlated with the worse prognosis of HCC patients. Overexpression of miR-505 suppressed the proliferation, colony formation and induced apoptosis of both HepG2 and Huh7 cells. Further mechanism study uncovered that miR-505 bound the 3′-untranslated region (3′-UTR) of the insulin growth factor receptor (IGF-1R) and inhibited the expression of IGF-1R in HCC cells. The down-regulation of IGF-1R by miR-505 further suppressed the phosphorylation of AKT at the amino acid S473. Consistently, the abundance of glucose transporter (GLUT) 1 (GLUT1) was reduced with the overexpression of miR-505. Down-regulation of GLUT1 by miR-505 consequently attenuated the glucose uptake, lactate production and ATP generation of HCC cells. Collectively, our results demonstrated the tumor suppressive function of miR-505 possibly via inhibiting the glycolysis of HCC cells. These findings suggested miR-505 as an interesting target for designing anti-cancer strategy in HCC.

Highlights

Hepatocellular carcinoma (HCC) is one of the most common malignancies with high mortality and occurrence around the world [1–3]
To illustrate the correlation between the expression of miR-505 and the clinical characteristics of HCC patients, all the 60 HCC patients were divided into miR-505-high or -low group according to the median value of miR-505 expression level
To evaluate whether the aberrant expression of miR-505 was a potential biomarker for the prognosis of HCC patients, log rank test was performed to analyze the correlation between the expression of miR-505 and the survival of HCC patients

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common malignancies with high mortality and occurrence around the world [1–3]. Diagnosis of HCC is difficult due to the lack of efficient biomarkers. It is urgent to identify novel factors and characterize the underlying mechanisms involved in the progression of HCC. MiRNAs play important roles in regulating gene expression by pairing with the 3 -untranslated region (3 -UTR) of target mRNAs, which results in their degradation or translation inhibition [7]. Dysfunction of miRNAs was associated with the formation and progression of human diseases, especially cancers [9–12]. Many miRNAs are aberrantly expressed in HCC and play important roles in the initiation and progression of cancer. MiR-1468 promoted HCC development via activating AKT signaling [13]. MiR-199 acted as a tumor suppressor in HCC by down-regulating the expression of regulators of G-protein signaling 17 [14].

Methods

Results

Conclusion