Growing evidence indicates that microRNAs have a significant role in tumor development and may constitute robust biomarkers for cancer diagnosis and prognosis. In this study, we evaluated the clinical and functional relevance of microRNA-122 (miR-122) expression in human hepatocellular carcinoma (HCC). We report that miR-122 is specifically repressed in a subset of primary tumors that are characterized by poor prognosis. We further show that the loss of miR-122 expression in tumor cells segregates with specific gene expression profiles linked to cancer progression, namely the suppression of hepatic phenotype and the acquisition of invasive properties. We identify liver-enriched transcription factors as central regulatory molecules in the gene networks associated with loss of miR-122, and provide evidence suggesting that miR-122 is under the transcriptional control of HNF1A, HNF3A and HNF3B. We further show that loss of miR-122 results in an increase of cell migration and invasion and that restoration of miR-122 reverses this phenotype. In conclusion, miR-122 is a marker of hepatocyte-specific differentiation and an important determinant in the control of cell migration and invasion. From a clinical point of view, our study emphasizes miR-122 as a diagnostic and prognostic marker for HCC progression.

Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties.

Background
Mutations and epigenetic aberrant signaling of growth factors pathways contribute to carcinogenesis. Recent studies reveal that non-coding RNAs are controllers of gene expression. H19 is an imprinted gene that demonstrates maternal monoallelic expression without a protein product; although its expression is shut off in most tissues postnatally, it is re-activated during adult tissue regeneration and tumorigenesis. Moreover, H19 is highly expressed in liver metastasis derived from a range of carcinomas. The objective of this study is to explore the role of H19 in carcinogenesis, and to determine its identification as an anti-tumor target.

/pdf/the-h19-non-coding-rna-is-essential-for-human-tumor-growth-2x1qs5ppdy.pdf

The H19 non-coding RNA is essential for human tumor growth.

An overview on manufactured nanoparticles in plants: Uptake, translocation, accumulation and phytotoxicity

Uptake, transport and toxicity of engineered nanomaterials (ENMs) into plant cells are complex processes that are currently still not well understood. Parts of this problem are the multifaceted pla...

Barriers, pathways and processes for uptake, translocation and accumulation of nanomaterials in plants – Critical review

1560 Epithelial cells require attachment to extra-cellular matrix (ECM) to suppress an apoptotic cell death program termed anoikis. We describe a non-apoptotic cell death program in matrix-detached cells, termed entosis, that is initiated by a previously unrecognized and unusual process involving the invasion of one cell into another, leading to a transient state in which a live cell is contained within a neighboring host cell. These 9cell-in-cell9 structures closely resemble similar cytological features in human cancers. Although a small percentage of live internalized cells can be released, the majority of internalized cells undergo non-apoptotic cell death by lysosomal acidification. Based on these data, we present evidence for a tumor suppressive role of entosis in human breast cancer. Paradoxically, we have also found that entosis can promote the development of aneuploidy, as live internalized cells can disrupt cytokinesis of host cells leading to multinucleation in vitro and in vivo. Thus, entosis may be tumor suppressive in some contexts and paradoxically tumor promoting in others. Models to investigate the role of entosis in human tumors will be presented.

A non-apoptotic cell death process, entosis, that occurs by cell-in-cell invasion.

Nearly 15 types of programmed cell death (PCD) have been identified to date. Among them, apoptosis is the most common and well-studied type of PCD. In this review, we discuss different apoptotic pathways in which plasma membrane and membrane organelles, such as mitochondria, endoplasmic reticulum, Golgi apparatus, lysosomes, and nucleus play the pivotal role. Data concerning caspase cascades involved in these mechanisms are described. Various apoptosis induction mechanisms are analyzed and compared. The close relations between them and the possibility of switching from one pathway to another are demonstrated. In most cases, the result of these pathways is mitochondrial membrane permeabilization and/or caspase activation. These two events are closely linked and serve as the central point of integration of the apoptotic cell death pathways.

Mechanisms of Apoptosis.

We have studied the effect of the engineered nanomaterial Taunit, containing multiwalled carbon nanotubes (MWCNTs), on the growth of Onobrychis arenaria seedlings and investigated whether affected plants uptake and accumulate MWCNTs. We found that 100 μg/mL and 1000 μg/mL of Taunit stimulated the growth of roots and stems, and enhanced the peroxidase activity in these parts of plants. Microscopy studies showed the presence of MWCNTs in the root and leaf tissues of seedlings exposed to Taunit, suggesting that MWCNTs have a capacity to penetrate the cell walls, accumulate in roots and translocate to the leaves. Thus the stimulating effect of MWCNTs on seedlings of O. arenaria may be associated with the primary uptake and accumulation of MWCNTs by plant roots followed by translocation to the other plant tissues.

https://rd.springer.com/content/pdf/10.1007%2Fs11705-012-1290-5.pdf

Uptake and accumulation of multiwalled carbon nanotubes change the morphometric and biochemical characteristics of Onobrychis arenaria seedlings

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.21293

Oncogene-specific gene expression signatures at preneoplastic stage in mice define distinct mechanisms of hepatocarcinogenesis.

Engineered nanoparticles (ENPs) are now being used in many sectors of industry; however, the impact of ENPs on the environment still requires further study, since their use, recycling, and accidental spill can result in the accumulation of nanoparticles in the atmosphere, soil, and water. Plants are an integral part of ecosystems; hence their interaction with ENPs is inevitable. It is important to understand the consequences of this interaction and assess its potential effects. The present research is focused on studying the effects of the industrial material Taunit, containing multi-walled carbon nanotubes (MWNTs), on plants, and testing of its ability to penetrate into plant cells and tissues. Taunit has been found to stimulate the growth of roots and stems and cause an increase in peroxidase activity in Onobrychis arenaria seedlings. Peroxidase activity increases with decreasing concentration of Taunit from 1,000 to 100 mg/l. MWNTs from Taunit were detected in the cells and tissues of seedling roots and leaves, implying the ability of MWNTs to penetrate into roots and accumulate there, as well as their ability to be transported into seedling leaves. Thus, the changes in the physiological parameters of plants are associated not only with MWNT adsorption on the root surface, as previously believed, but also with their penetration, uptake and accumulation in the plant cells and tissues.

https://actanaturae.ru/2075-8251/article/download/10700/pdf

Multi-walled Сarbon Nanotubes Penetrate into Plant Cells and Affect the Growth of Onobrychis arenaria Seedlings.

The presence of micronuclei in a cell is an indicator of DNA damage and genetic instability. In this review, mechanisms of emergence of micronuclei, their functional activity, and pathways of elimination are discussed. It is supposed that morphological and functional varieties of micronuclei as well as their degradation pathways can be determined by the chromosomal material localized inside these cell structures.

G. E. Onishchenko

Papers

Mechanisms of Apoptosis.

Uptake and accumulation of multiwalled carbon nanotubes change the morphometric and biochemical characteristics of Onobrychis arenaria seedlings

Oncogene-specific gene expression signatures at preneoplastic stage in mice define distinct mechanisms of hepatocarcinogenesis.

Multi-walled Сarbon Nanotubes Penetrate into Plant Cells and Affect the Growth of Onobrychis arenaria Seedlings.

Biogenesis of Micronuclei.