Abstract
Hepatocellular carcinoma (HCC) is one of the top causes of cancer mortality worldwide. Although HCC has been researched extensively, there is still a need for novel and effective therapeutic interventions. There is substantial evidence that initiation of carcinogenesis in liver cirrhosis, a leading cause of HCC, is mediated by cancer stem cells (CSCs). CSCs were also shown to be responsible for relapse and chemoresistance in several cancers, including HCC. MicroRNAs (miRNAs) constitute important epigenetic markers that regulate carcinogenesis by acting post-transcriptionally on mRNAs, contributing to the progression of HCC. We have previously shown that co-culture of cancer cells with mesenchymal stem cells (MSCs) could induce the reprogramming of MSCs into CSC-like cells. In this review, we evaluate the available data concerning the epigenetic regulation of miRNAs through methylation and the possible role of this regulation in stem cell and somatic reprogramming in HCC.
Highlights
Downregulated (Huang et al, 2009) Involved in enhancing proliferation and carcinogenesis (Caruso et al, 2012) miR-200b suppressed the expression of BMI1 and ZEB1, ZEB1 promotes CD13, CD24, and EPCAM resulting in the upregulation of CD13 and CD24 so, the miR-200-ZEB1 circuit regulates stemness in Hepatocellular carcinoma (HCC) and differentiates between HCC contains CD13+/CD24+ cancer stem cells (CSCs) from EpCAM + CSCs (Tsai et al, 2017)
Studies from our laboratory have shown that soluble HCC factors play a vital role in the induction of chemoresistance properties in human bone marrow-mesenchymal stem cells (MSCs) and trigger their transformation into CSC-like cells (El-Badawy et al, 2017)
The initiation of HCC is known to be preceded by cirrhosis, the initiation mechanism itself is thought to involve CSCs
Summary
Hepatocellular carcinoma (HCC) is the most frequent primary malignancy of the liver. It is the third leading cause of mortality associated with cancer worldwide (Yang and Roberts, 2010; Dhanasekaran et al, 2012). HCC is a multifactorial disease that is influenced by several risk factors It typically develops as a result of underlying liver disease and is commonly associated with cirrhosis (Huang et al, 2013). Obesity is one of the highly recent factors that plays a significant role in developing non-alcoholic fatty liver disease (NAFLD) (Cholankeril et al, 2017). It can progress in many stages starting with lipid deposition in hepatocytes’ cytoplasm and can lead to non-alcoholic steatohepatitis (NASH) (Marrero et al, 2002; Guzman et al, 2008; Reddy et al, 2012; White et al, 2012). The Wnt/β-catenin signaling pathway seems to play major roles in the development of CSCs and in self-renewal, tumorigenesis, and cancer chemoresistance (Espada et al, 2009; Eaves and Humphries, 2010; Mohammed et al, 2016)
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