Mechanisms of HBV-induced hepatocellular carcinoma

https://www.journal-of-hepatology.eu/article/S0168-8278(14)00731-4/pdf

miR-122 – A key factor and therapeutic target in liver disease

Hepatocellular carcinoma (HCC) is a leading lethal malignancy worldwide. However, the molecular mechanisms underlying liver carcinogenesis remain poorly understood. Over the past two decades, overwhelming evidence has demonstrated the regulatory roles of different classes of non-coding RNAs (ncRNAs) in liver carcinogenesis related to a number of aetiologies, including HBV, HCV and NAFLD. Among the ncRNAs, microRNAs, which belong to a distinct class of small ncRNAs, have been proven to play a crucial role in the post-transcriptional regulation of gene expression. Deregulation of microRNAs has been broadly implicated in the inactivation of tumour-suppressor genes and activation of oncogenes in HCC. Modern high-throughput sequencing analyses have unprecedentedly identified a very large number of non-coding transcripts. Divergent groups of long ncRNAs have been implicated in liver carcinogenesis through interactions with DNA, RNA or proteins. Overall, ncRNAs represent a burgeoning field of cancer research, and we are only beginning to understand the importance and complicity of the ncRNAs in liver carcinogenesis. In this Review, we summarize the common deregulation of small and long ncRNAs in human HCC. We also comprehensively review the pathological roles of ncRNAs in liver carcinogenesis, epithelial-to-mesenchymal transition and HCC metastasis and discuss the potential applications of ncRNAs as diagnostic tools and therapeutic targets in human HCC.

Non-coding RNAs in hepatocellular carcinoma: molecular functions and pathological implications

Because of its unique function and anatomical location, the liver is exposed to a multitude of toxins and xenobiotics, including medications and alcohol, as well as to infection by hepatotropic viruses, and therefore, is highly susceptible to tissue injury. Cell death in the liver occurs mainly by apoptosis or necrosis, with apoptosis also being the physiologic route to eliminate damaged or infected cells and to maintain tissue homeostasis. Liver cells, especially hepatocytes and cholangiocytes, are particularly susceptible to death receptor-mediated apoptosis, given the ubiquitous expression of the death receptors in the organ. In a quite unique way, death receptor-induced apoptosis in these cells is mediated by both mitochondrial and lysosomal permeabilization. Signaling between the endoplasmic reticulum and the mitochondria promotes hepatocyte apoptosis in response to excessive free fatty acid generation during the metabolic syndrome. These cell death pathways are partially regulated by microRNAs. Necrosis in the liver is generally associated with acute injury (i.e., ischemia/reperfusion injury) and has been long considered an unregulated process. Recently, a new form of "programmed" necrosis (named necroptosis) has been described: the role of necroptosis in the liver has yet to be explored. However, the minimal expression of a key player in this process in the liver suggests this form of cell death may be uncommon in liver diseases. Because apoptosis is a key feature of so many diseases of the liver, therapeutic modulation of liver cell death holds promise. An updated overview of these concepts is given in this article.

/pdf/apoptosis-and-necrosis-in-the-liver-4sjdni6rar.pdf

Apoptosis and necrosis in the liver.

The effective and efficient management of cancer patients relies upon early diagnosis and/or the monitoring of treatment, something that is often difficult to achieve using standard tissue biopsy techniques. Biological fluids such as blood hold great possibilities as a source of non-invasive cancer biomarkers that can act as surrogate markers to biopsy-based sampling. The non-invasive nature of these “liquid biopsies” ultimately means that cancer detection may be earlier and that the ability to monitor disease progression and/or treatment response represents a paradigm shift in the treatment of cancer patients. Below, we review one of the most promising classes of circulating cancer biomarkers: microRNAs (miRNAs). In particular, we will consider their history, the controversy surrounding their origin and biology, and, most importantly, the hurdles that remain to be overcome if they are really to become part of future clinical practice.

https://www.mdpi.com/1422-0067/17/5/627/pdf

New Concepts in Cancer Biomarkers: Circulating miRNAs in Liquid Biopsies

https://www.journal-of-hepatology.eu/article/S0168-8278(10)00186-8/pdf

London L.P. Jooi

Papers

Lethal-7 is down-regulated by the hepatitis B virus x protein and targets signal transducer and activator of transcription 3