Role of Micro-RNA in the Regulation of Cell Polarization in Hepatocellular Carcinoma

Abstract

The occurrence of tissue scarring and architecture-modifying signaling led to a tumorigenic microenvironment. Targeting specifically the biological mediators responsible for the physiological and morphological changes accommodating hepatocellular carcinoma (HCC) growth may be the key for identifying a future HCC cure. Morphological and physiological features of cultured HepG2 cells in both stimulated recombinant human vascular endothelial growth factor (VEGF165) and unstimulated (control) conditions were assessed. Quantitative reverse transcription (RT)-PCR measured endogenous VEGF expression levels. The assessment of proangiogenic biological mediator (micro RNA [miR]-296, miR-31, and miR-17) profiles was achieved by polarization-inducing VEGF165 stimulation followed by quantitative RT-PCR. In vitro conditions reproduced successfully the physiological environment leading to the occurrence of HCC, including the successful HepG2 polarization following VEGF stimulation. While endogenous VEGF production only occurs if complete polarization has been reached, the quantified biological mediator profiles determined here pointed at either possible early stages of depolarization or at the lack of tumorigenic potential of the HepG2 cells. All tested miRs displayed upregulated profiles, although miR-296 was less amplified (3.78-fold compared with control) than miR-31 or miR-17 (6.5- and 6.6-fold, respectively). The findings surrounding miR-17 reproduce similar data reported in the literature; the unexpected high miR-31 expression was intriguing. Given HepG2 cells' minimal tumorigenic potential, the unexpected multifold upregulation of miR-31 may be a cause or a consequence of HepG2 cells' low tumorigenic potential. The exploration of miR-31 therapeutic potential may be a future rewarding endeavor.