https://hal-univ-rennes1.archives-ouvertes.fr/hal-01834480/document

Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease

The role of MAPK signalling pathways in the response to endoplasmic reticulum stress

Aberrant overexpression of the long non-coding RNA NEAT1 (nuclear paraspeckle assembly transcript 1) has been documented in different types of solid tumours, such as lung cancer, oesophageal cancer, colorectal cancer and hepatocellular carcinoma, in which its high levels are associated with poor prognosis. In contrast, NEAT1 is downregulated in acute promyelocytic leukaemia where it promotes leucocyte differentiation. In this review, we provide an overview of current evidence concerning the oncogenic role and potential clinical utilities of NEAT1. Further investigations are warranted to elucidate the upstream and downstream mechanisms of NEAT1 overexpression.

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NEAT1: A novel cancer-related long non-coding RNA.

The nuclear paraspeckle assembly transcript 1 (NEAT1, a long non-coding RNA) is frequently overexpressed in human tumors, and higher NEAT1 expression is correlated with worse survival in cancer patients. NEAT1 drives tumor initiation and progression by modulating the expression of genes involved in the regulation of tumor cell growth, migration, invasion, metastasis, epithelial-to-mesenchymal transition, stem cell-like phenotype, chemoresistance and radioresistance, indicating the potential for NEAT1 to be a novel diagnostic biomarker and therapeutic target. Mechanistically, NEAT1 functions as a scaffold RNA molecule by interacting with EZH2 (a subunit of the polycomb repressive complex) to influence the expression of downstream effectors of EZH2, it also acts as a microRNA (miRNA) sponge to suppress the interactions between miRNAs and target mRNAs, and affects the expression of miR-129 by promoting the DNA methylation of the miR-129 promoter region. Knockdown of NEAT1 via small interfering RNA or short hairpin RNA inhibits the malignant behavior of tumor cells. In this review, we highlight the latest insights into the expression pattern, biological roles and mechanisms underlying the function and regulation of NEAT1 in tumors, and especially focus on its clinical implication as a new diagnostic biomarker and an attractive therapeutic target for cancers.

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Long Non-coding RNA NEAT1: A Novel Target for Diagnosis and Therapy in Human Tumors.

Peroxiredoxins (PRDXs) are a ubiquitously expressed family of small (22-27 kDa) non-seleno peroxidases that catalyze the peroxide reduction of H2O2, organic hydroperoxides and peroxynitrite. They are highly involved in the control of various physiological functions, including cell growth, differentiation, apoptosis, embryonic development, lipid metabolism, the immune response, as well as cellular homeostasis. Although the protective role of PRDXs in cardiovascular and neurological diseases is well established, their role in cancer remains controversial. Increasing evidence suggests the involvement of PRDXs in carcinogenesis and in the development of drug resistance. Numerous types of cancer cells, in fact, are characterized by an increase in reactive oxygen species (ROS) production, and often exhibit an altered redox environment compared with normal cells. The present review focuses on the complex association between oxidant balance and cancer, and it provides a brief account of the involvement of PRDXs in tumorigenesis and in the development of chemoresistance.

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The role of peroxiredoxins in cancer (Review)

Esophageal squamous carcinoma (ESCC) may be developed through a progressive sequence from mild to severe dysplasia, carcinoma in situ, and finally, invasive carcinoma. Chemoprevention can block or weaken the influence of development. Recent study has shown luteolin, a bioflavonoid, possesses anti-inflammatory, antioxidant, and anti-proliferative effects, and it might have a preventive effect in this progress. In this study, we focused on the effect of luteolin on cell cycle regulation in human Esophageal Squamous Carcinoma Cell Line EC1 and KYSE450 Cells in vitro and its potential mechanisms. Observations by flow cytometer showed that luteolin inhibited cell cycle progression at G2/M phase in a dose- and time-dependent manner. We also found that luteolin could induce cell apoptosis via decreasing activation of caspase-3 and down-regulation of mitochondrial membrane potential. Western blot results showed the protein expression of cycle related protein CyclinD1 and apoptosis related proteins caspase-3, caspase-9, and Bak were also significantly decreased in luteolin treated cells compared with the non-luteolin treated cells. Our results suggest that the proper use of luteolin might be a practical approach to the prevention of esophageal carcinoma via the inhibition of cell proliferation and other potential high risk regions for this disease. Citation Format: Ping Chen, Tao Hu, Yane Ma, Xiaoyu Chen, Liping Dai, Ningjing Lei, Ziming Dong, Pei Li. Luteolin inhibits cell proliferation and induces cell apoptosis via down-regulation of mitochondrial membrane potential in esophageal carcinoma cells EC1 and KYSE450. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2808. doi:10.1158/1538-7445.AM2015-2808

Abstract 2808: Luteolin inhibits cell proliferation and induces cell apoptosis via down-regulation of mitochondrial membrane potential in esophageal carcinoma cells EC1 and KYSE450

Peroxiredoxin 1 (Prdx1) is an antioxidant and plays an important role in H2O2-mediated cell signaling. We previously found that the expression level of Prdx1 was elevated in esophagus squamous cell carcinoma (ESCC) tissue using a proteomics approach. Since overexpressed protein can induce an autoimmune response, to further examine whether serum from ESCC patients exhibits immunoreactivity against Prdx1, autoantibody responses to Prdx1 were evaluated by ELISA, western blotting and indirect immunofluorescence assay in sera from patients with ESCC and normal individuals. Immunohistochemical study with tissue array slides and western blot analysis with cancer cell lines were also performed to analyze the protein expression profiles of Prdx1 in ESCC tissues and cancer cell lines. The results demonstrated that the positive rate of autoantibody against Prdx1 in ESCC sera was 13.2% (9/68), whereas this rate was 0% (0/89) in normal individuals. Data also showed that expression of Prdx1 was significantly increased in ESCC tissues when compared to expression in paired adjacent normal tissues (P<0.05). The data indicate that Prdx1 may contribute to malignant transformation of the esophagus, and may be used as a biomarker in the immunodiagnosis of ESCC.

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Peroxiredoxin 1 is a tumor-associated antigen in esophageal squamous cell carcinoma.

Hepatocellular carcinoma (HCC) is a type of cancer with a very poor prognosis. Although α-fetoprotein (AFP) is the most effective marker available to detect HCC, the sensitivity and specificity are not optimal. Therefore, there is a need for the development of more sensitive and specific methods that can supplement AFP in the early detection of this cancer. In this study, autoantibody responses to glucose-regulated protein 78 (GRP78) were evaluated by enzyme-linked immunosorbent assay (ELISA), western blotting and indirect immunofluorescence assay in sera from patients with HCC, liver cirrhosis (LC) and chronic hepatitis (CH), as well as from normal human individuals. Immunohistochemistry (IHC) with tissue array slides was also preformed to analyze protein expression profiles of GRP78 in HCC and control tissues. The prevalence of autoantibodies against GRP78 was 35.5% (27/76) in HCC, which was significantly higher than that in LC, CH and normal human sera (NHS; P<0.01). The average titer of autoantibodies against GRP78 in HCC sera was higher compared to that in LC, CH and NHS(P<0.01). When both autoantibodies against GRP78 and AFP were used simultaneously as diagnostic markers, sensitivity reached 71.4%. Our data indicate that anti-GRP78 autoantibodies may be potential diagnostic markers for HCC, especially in conjunction with AFP.

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Autoantibodies against glucose-regulated protein 78 as serological diagnostic biomarkers in hepatocellular carcinoma.

Tumor-associated antigens (TAAs) recognized by cellular and/or humoral effectors of the immune system are attractive targets for diagnostic and therapeutic approaches to human cancer. Different approaches can be used to comprehensively characterize and validate the identified TAA/anti-TAA systems, which are potential biomarkers in cancer immunodiagnosis. Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The high fatality rate of HCC within one year after its detection might be partly attributed to a lack of diagnostic methods that enable the early detection. Our previous studies have shown that novel autoantibodies can appear which are not detected prior to pre-malignant conditions during transition from chronic liver disease to HCC. The hypothesis we advance is the transition to malignancy can be associated with autoantibody response to certain cellular proteins that might have some role in tumorigenesis. We propose that the information that the cancer patient’s immune system is conveying in the form of autoantibodies to tumor-associated antigens (TAAs) should be utilized to a greater extent in identifying early signs of tumorigenesis. In this review, we will focus on the important features of TAA and the possibility that autoantibodies to TAAs can be used as biomarkers in immunodiagnosis and prognosis of HCC.

/pdf/autoantibodies-to-tumor-associated-antigens-as-biomarkers-in-43sxhxtrck.pdf

Autoantibodies to tumor-associated antigens as biomarkers in human hepatocellular carcinoma (HCC)

Chemoresistance and metastasis are the major challenges for the current ovarian cancer treatment. Understanding the mechanisms of ovarian cancer progression and metastasis is critically important for developing novel therapies. The advances in extracellular vesicles (EVs) research in recent years have attracted extensive attention. EVs contain a variety of proteins, RNAs, DNAs, and metabolites. Accumulating evidence indicates that ovarian cancer cells secrete a large amount of EVs, playing an important role in tumor progression and recurrence. In the microenvironment of ovarian tumor, EVs participate in the information transmission between stromal cells and immune cells, promoting the immune escape of ovarian cancer cells and facilitating cancer metastasis. Here, we review the recent advances of EVs in chemoresistance, mechanisms of metastasis, and immune evasion of ovarian cancer. Furthermore, we also discuss the challenges of EV research and future application of EVs as promising biomarker sources in response to therapy and in therapy-delivery approaches for ovarian cancer patients. 

/pdf/extracellular-vesicles-in-ovarian-cancer-chemoresistance-35pamsck.pdf

Ningjing Lei

Papers

Abstract 2808: Luteolin inhibits cell proliferation and induces cell apoptosis via down-regulation of mitochondrial membrane potential in esophageal carcinoma cells EC1 and KYSE450

Peroxiredoxin 1 is a tumor-associated antigen in esophageal squamous cell carcinoma.

Autoantibodies against glucose-regulated protein 78 as serological diagnostic biomarkers in hepatocellular carcinoma.

Autoantibodies to tumor-associated antigens as biomarkers in human hepatocellular carcinoma (HCC)

Extracellular vesicles in ovarian cancer chemoresistance, metastasis, and immune evasion