MicroRNA-152-mediated dysregulation of hepatic transferrin receptor 1 in liver carcinogenesis

Abstract

Over-expression of transferrin receptor 1 (TFRC) is observed in hepatocellular carcinoma (HCC); however, there is a lack of conclusive information regarding the mechanisms of this dysregulation. In the present study, we demonstrated a significant increase in the levels of TFRC mRNA and protein in preneoplastic livers from relevant experimental models of human hepatocarcinogenesis and in human HCC cells. Additionally, using the TCGA database, we demonstrated an over-expression of TFRC in human HCC tissue samples and a markedly decreased level of microRNA-152 (miR-152) when compared to non-tumor liver tissue. The results indicated that the increase in levels of TFRC in human HCC cells and human HCC tissue samples may be attributed, in part, to a post-transcriptional mechanism mediated by a down-regulation of miR-152. This was evidenced by a strong inverse correlation between the level of TFRC and the expression of miR-152 in human HCC cells (r = −0.99, p = 4. 7 × 10−9), and was confirmed by in vitro experiments showing that transfection of human HCC cell lines with miR-152 effectively suppressed TFRC expression. This suggests that miR-152-specific targeting of TFRC may provide a selective anticancer therapeutic approach for the treatment of HCC.

MicroRNA‑138 targets SP1 to inhibit the proliferation, migration and invasion of hepatocellular carcinoma cells

“…It was reported that there were 782,500 new HCC cases and 745,500 incidences of mortality due to HCC worldwide during 2012, of which half were in China (2). Numerous risk factors for HCC patients have been identified, including chronic viral hepatitis B or C infection, chemical exposure, alcohol consumption, obesity, hereditary hemochromatosis and hepatosteatosis (3). At present, the primary therapeutic strategies for HCC are surgical resection, liver transplantation and ablation, and chemotherapy (4).…”

Transferrin receptor 1 overexpression is associated with tumour de‐differentiation and acts as a potential prognostic indicator of hepatocellular carcinoma

“…MicroRNA‐152 can inhibit cell growth in HepG2 and Hep3B cells . MicroRNA‐152 also suppressed TFR‐1 gene expression in HepG2 . Inhibition of TFR‐1 expression by increased microRNA‐152 in HepG2 cells was associated with decreased intracellular iron and tumorigenicity .…”

“…29 MicroRNA-152 also suppressed TFR-1 gene expression in HepG2. 30 Inhibition of TFR-1 expression by increased microRNA-152 in HepG2 cells was associated with decreased intracellular iron and tumorigenicity. 30 In this previous study, based on The Cancer Genome Atlas (TCGA) databases of human HCC, TFR-1 expression increased with the progression of HCC and TFR-1 expression was inversely correlated with microRNA-152.…”

“…30 Inhibition of TFR-1 expression by increased microRNA-152 in HepG2 cells was associated with decreased intracellular iron and tumorigenicity. 30 In this previous study, based on The Cancer Genome Atlas (TCGA) databases of human HCC, TFR-1 expression increased with the progression of HCC and TFR-1 expression was inversely correlated with microRNA-152. 30 Moreover, HCV core protein is a potential down-regulator of microRNA-152, 31 and DNA methylation in HBV-related HCC is induced by down-regulation of microRNA-152.…”

Blocking transferrin receptor inhibits the growth of lung adenocarcinoma cells in vitro

“…However, there is evidence that TfR has many other biological roles in addition to its primary function of facilitating iron transport and metabolism, such as its profound effect on mammalian cell growth and productivity . TfR expression is normally restricted to a limited number of sites in humans, including basal keratinocytes of the epidermis; islet cells of the pancreas; and parenchymal cells of the liver, testis, and pituitary gland . In healthy lung tissue, airway and alveolar epithelia and bronchial glands do not express TfR .…”