scholarly journals Non-Genomic Control of Dynamic MYCN Gene Expression in Liver Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Xian-Yang Qin ◽  
Luc Gailhouste

Upregulated MYCN gene expression is restricted to specialized cell populations such as EpCAM+ cancer stem cells in liver cancer, regardless of DNA amplification and mutation. Here, we reviewed the role of MYCN gene expression in liver homeostasis, regeneration, and tumorigenesis, and discussed the potential non-genomic mechanisms involved in controlling MYCN gene expression in liver cancer, with a focus on inflammation-mediated signal transduction and microRNA-associated post-transcriptional regulation. We concluded that dynamic MYCN gene expression is an integrated consequence of multiple signals in the tumor microenvironment, including tumor growth-promoting signals, lipid desaturation-mediated endoplasmic reticulum stress adaptation signals, and tumor suppressive miRNAs, making it a potential predictive biomarker of tumor stemness and plasticity. Therefore, understanding and tracing the dynamic changes and functions of MYCN gene expression will shed light on the origin of liver tumorigenesis at the cellular level and the development of novel therapeutic and diagnostic strategies for liver cancer treatment.

Plants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 466
Author(s):  
Marie-Christine Carpentier ◽  
Cécile Bousquet-Antonelli ◽  
Rémy Merret

The recent development of high-throughput technologies based on RNA sequencing has allowed a better description of the role of post-transcriptional regulation in gene expression. In particular, the development of degradome approaches based on the capture of 5′monophosphate decay intermediates allows the discovery of a new decay pathway called co-translational mRNA decay. Thanks to these approaches, ribosome dynamics could now be revealed by analysis of 5′P reads accumulation. However, library preparation could be difficult to set-up for non-specialists. Here, we present a fast and efficient 5′P degradome library preparation for Arabidopsis samples. Our protocol was designed without commercial kit and gel purification and can be easily done in one working day. We demonstrated the robustness and the reproducibility of our protocol. Finally, we present the bioinformatic reads-outs necessary to assess library quality control.


Oncogene ◽  
2021 ◽  
Author(s):  
Biswajyoti Sahu ◽  
Päivi Pihlajamaa ◽  
Kaiyang Zhang ◽  
Kimmo Palin ◽  
Saija Ahonen ◽  
...  

AbstractCancer is the most complex genetic disease known, with mutations implicated in more than 250 genes. However, it is still elusive which specific mutations found in human patients lead to tumorigenesis. Here we show that a combination of oncogenes that is characteristic of liver cancer (CTNNB1, TERT, MYC) induces senescence in human fibroblasts and primary hepatocytes. However, reprogramming fibroblasts to a liver progenitor fate, induced hepatocytes (iHeps), makes them sensitive to transformation by the same oncogenes. The transformed iHeps are highly proliferative, tumorigenic in nude mice, and bear gene expression signatures of liver cancer. These results show that tumorigenesis is triggered by a combination of three elements: the set of driver mutations, the cellular lineage, and the state of differentiation of the cells along the lineage. Our results provide direct support for the role of cell identity as a key determinant in transformation and establish a paradigm for studying the dynamic role of oncogenic drivers in human tumorigenesis.


2019 ◽  
Vol 84 (6) ◽  
pp. 233-239
Author(s):  
Xu Hui ◽  
Hisham Al-Ward ◽  
Fahmi Shaher ◽  
Chun-Yang Liu ◽  
Ning Liu

<b><i>Background:</i></b> MicroRNAs (miRNAs) represent a group of non-coding RNAs measuring 19–23 nucleotides in length and are recognized as powerful molecules that regulate gene expression in eukaryotic cells. miRNAs stimulate the post-transcriptional regulation of gene expression via direct or indirect mechanisms. <b><i>Summary:</i></b> miR-210 is highly upregulated in cells under hypoxia, thereby revealing its significance to cell endurance. Induction of this mRNA expression is an important feature of the cellular low-oxygen response and the most consistent and vigorous target of HIF. <b><i>Key Message:</i></b> miR-210 is involved in many cellular functions under the effect of HIF-1α, including the cell cycle, DNA repair, immunity and inflammation, angiogenesis, metabolism, and macrophage regulation. It also plays an important regulatory role in T-cell differentiation and stimulation.


2010 ◽  
Vol 38 (1) ◽  
pp. 217-222 ◽  
Author(s):  
Ini-Isabée Witzel ◽  
Li Fang Koh ◽  
Neil D. Perkins

Cyclin D1 is a key regulator of cell proliferation and its expression is subject to both transcriptional and post-transcriptional regulation. In different cellular contexts, different pathways assume a dominant role in regulating its expression, whereas their disregulation can contribute to overexpression of cyclin D1 in tumorigenesis. Here, we discuss the ability of the NF-κB (nuclear factor κB)/IKK [IκB (inhibitor of NF-κB) kinase] pathways to regulate cyclin D1 gene transcription and also consider the newly discovered role of the SNARP (SNIP1/SkIP-associated RNA processing) complex as a co-transcriptional regulator of cyclin D1 RNA stability.


Author(s):  
Kévin Tartour ◽  
Kiran Padmanabhan

Circadian rhythms orchestrate organismal physiology and behavior in order to anticipate daily changes in the environment. Virtually all cells have an internal rhythm that is synchronized every day by Zeitgebers (environmental cues). The synchrony between clocks within the animal enables the fitness and the health of organisms. Conversely, disruption of rhythms is linked to a variety of disorders: aging, cancer, metabolic diseases, and psychological disorders among others. At the cellular level, mammalian circadian rhythms are built on several layers of complexity. The transcriptional-translational feedback loop (TTFL) was the first to be described in the 90s. Thereafter oscillations in epigenetic marks highlighted the role of chromatin state in organizing the TTFL. More recently, studies on the 3D organization of the genome suggest that genome topology could be yet another layer of control on cellular circadian rhythms. The dynamic nature of genome topology over a solar day implies that the 3D mammalian genome has to be considered in the fourth dimension-in time. Whether oscillations in genome topology are a consequence of 24 h gene-expression or a driver of transcriptional cycles remains an open question. All said and done, circadian clock-gated phenomena such as gene expression, DNA damage response, cell metabolism and animal behavior—go hand in hand with 24 h rhythms in genome topology.


Cancers ◽  
2013 ◽  
Vol 6 (1) ◽  
pp. 28-41 ◽  
Author(s):  
Thoria Diab ◽  
Naima Hanoun ◽  
Christophe Bureau ◽  
Camille Christol ◽  
Louis Buscail ◽  
...  

2021 ◽  
Author(s):  
Chaoxiang Lv ◽  
Qiqi Zhang ◽  
Yuanguo Li ◽  
Entao Li ◽  
Fangxu Li ◽  
...  

Abstract M2 isoform of pyruvate kinase (PKM2) plays an important role in reprogramming of cell metabolism which is a hall-marker of tumorigenesis. PKM2 expression altering is closely related to cancer metabolism and tumor growth. In the present study, we analyzed the role of PKM2 expression in liver cancer in order to clarify its potential application value in the diagnosis and prognosis of liver cancer patients. In cancerous liver tissues, the PKM2 expression was significantly higher than normal tissues. High PKM2 expressing was related to patient’s age, gender, histological type, grade, stage, T classification and poor survival. Patients with Higher PKM2 expression had a shorter OS (P = 0.0013) and RFS (P = 0.027). ROC and Multivariate Cox analysis showed that high PKM2expression was a risk factor for patients’ poor prognosis. GSEA identified mitotic spindle, PI3K/Akt/mTOR signaling, notch signaling, apoptosis, G2M checkpoint and Wnt/β- Cantenin signaling were enriched with high PKM2 expression phenotype. These findings suggested PKM2 expression has potential as a predictive biomarker for the diagnosis and prognosis of patients with liver cancer.


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