scholarly journals SnoRNA in Cancer Progression, Metastasis and Immunotherapy Response

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 809
Author(s):  
Jildou van der Werf ◽  
Chue Vin Chin ◽  
Nicholas Ian Fleming
Keyword(s):  
Cancer Progression ◽  
Drug Targets ◽  
Cell Function ◽  
Immune Cell ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Cancer Types ◽  
Target Rna ◽  
Nucleolar Rna ◽  
Mtor Signalling

Small nucleolar RNA (snoRNA) were one of our earliest recognised classes of non-coding RNA, but were largely ignored by cancer investigators due to an assumption that their activities were confined to the nucleolus. However, as full genome sequences have become available, many new snoRNA genes have been identified, and multiple studies have shown their functions to be diverse. The consensus now is that many snoRNA are dysregulated in cancers, are differentially expressed between cancer types, stages and metastases, and they can actively modify disease progression. In addition, the regulation of the snoRNA class is dominated by the cancer-supporting mTOR signalling pathway, and they may have particular significance to immune cell function and anti-tumour immune responses. Given the recent advent of therapeutics that can target RNA molecules, snoRNA have robust potential as drug targets, either solely or in the context of immunotherapies.

scholarly journals NEAT1 and Paraspeckles in Cancer Development and Chemoresistance

2020 ◽  
Vol 6 (4) ◽  
pp. 43
Author(s):  
Gabriel Pisani ◽  
Byron Baron
Keyword(s):  
Cancer Progression ◽  
Drug Targets ◽  
Cellular Biology ◽  
Diverse Range ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Wide Range ◽  
Protein Research ◽  
The Stability ◽  
Abundant Transcript

Non-coding RNA were previously thought to be biologically useless molecules arising from simple transcriptional noise. These are now known to be an integral part of cellular biology and pathology. The wide range of RNA molecules have a diverse range of structures, functions, and mechanisms of action. However, structural long non-coding RNAs (lncRNAs) are a particular class of ncRNA that are proving themselves more and more important in cellular biology, as the exact structures that such RNAs form and stabilise become more understood. Nuclear Enriched Abundant Transcript 1 (NEAT1) is a specific structural RNA emerging as a critical component in the progress and development of cancer. NEAT1 forms part of multiple biological pathways, acting through a diverse group of mechanisms. The most important of these is the formation of the paraspeckle, through which it can influence the stability of a tumour to develop resistance to drugs. This review will thus cover the range of effects by which NEAT1 interacts with cancer progression in order to describe the various roles of NEAT1 in chemoresistance, as well as to identify drug targets that protein research alone could not provide.

scholarly journals Pan-cancer systematic identification of lncRNAs associated with cancer prognosis

2018 ◽  
Author(s):  
Matthew H. Ung ◽  
Evelien Schaafsma ◽  
Daniel E. Mattox ◽  
George L. Wang ◽  
Chao Cheng
Keyword(s):  
Drug Targets ◽  
Patient Survival ◽  
Cancer Prognosis ◽  
Rna Seq ◽  
Non Coding Rna ◽  
Cancer Types ◽  
Microarray Studies ◽  
Systematic Identification ◽  
Pan Cancer ◽  
Novel Associations

AbstractThe “dark matter” of the genome harbors several non-coding RNA species including IncRNAs, which have been implicated in neoplasias but remain understudied. RNA-seq has provided deep insights into the nature of lncRNAs in cancer but current RNA-seq data are rarely accompanied by longitudinal patient survival information. In contrast, a plethora of microarray studies have collected these clinical metadata that can be leveraged to identify novel associations between gene expression and clinical phenotypes. In this study, we developed an analysis framework that computationally integrates RNA-seq and microarray data to systematically screen 9,463 lncRNAs for association with mortality risk across 20 cancer types. In total, we identified a comprehensive list of associations between lncRNAs and patient survival and demonstrate that these prognostic lncRNAs are under selective pressure and may be functional. Our results provide valuable insights that facilitate further exploration of lncRNAs and their potential as cancer biomarkers and drug targets.

scholarly journals Pan-cancer systematic identification of lncRNAs associated with cancer prognosis

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8797 ◽  
Author(s):  
Matthew Ung ◽  
Evelien Schaafsma ◽  
Daniel Mattox ◽  
George L. Wang ◽  
Chao Cheng
Keyword(s):  
Drug Targets ◽  
Patient Survival ◽  
Cancer Prognosis ◽  
Rna Seq ◽  
Non Coding Rna ◽  
Cancer Types ◽  
Non Coding Rnas ◽  
Microarray Studies ◽  
Systematic Identification ◽  
Pan Cancer

Background The “dark matter” of the genome harbors several non-coding RNA species including Long non-coding RNAs (lncRNAs), which have been implicated in neoplasia but remain understudied. RNA-seq has provided deep insights into the nature of lncRNAs in cancer but current RNA-seq data are rarely accompanied by longitudinal patient survival information. In contrast, a plethora of microarray studies have collected these clinical metadata that can be leveraged to identify novel associations between gene expression and clinical phenotypes. Methods In this study, we developed an analysis framework that computationally integrates RNA-seq and microarray data to systematically screen 9,463 lncRNAs for association with mortality risk across 20 cancer types. Results In total, we identified a comprehensive list of associations between lncRNAs and patient survival and demonstrate that these prognostic lncRNAs are under selective pressure and may be functional. Our results provide valuable insights that facilitate further exploration of lncRNAs and their potential as cancer biomarkers and drug targets.

scholarly journals Up-regulation of long non-coding RNA SNHG20 promotes ovarian cancer progression via Wnt/β-catenin signaling

2018 ◽  
Vol 38 (1) ◽  
Author(s):  
Shanyang He ◽  
Yunhe Zhao ◽  
Xiaoping Wang ◽  
Yalan Deng ◽  
Zhiyong Wan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Target Gene ◽  
Biological Function ◽  
Downstream Target ◽  
Non Coding Rna ◽  
Downstream Target Gene ◽  
Long Non Coding Rna ◽  
Nucleolar Rna ◽  
Signaling Activity

Long non-coding RNA small nucleolar RNA host gene 20 (SNHG20) has been demonstrated to play crucial regulatory roles in many types of cancer. However, the biological function of long ncRNA (lncRNA) SNHG20 in ovarian cancer is still unclear. In the present study, we found that lncRNA SNHG20 was significantly increased in ovarian cancer. In addition, lncRNA SNHG20 knockdown suppressed the ovarian cancer progression, whereas overexpression of SNHG20 showed the opposite effects. Moreover, our results also revealed that lncRNA SNHG20 knockdown inhibited Wnt/β-catenin signaling activity by suppressing β-catenin expression and reversing the downstream target gene expression. Taken together, lncRNA SNHG20 plays an pivotal role in ovarian cancer progression by regulating Wnt/β-catenin signaling.

scholarly journals Hypoxia/HIF Modulates Immune Responses

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 260
Author(s):  
Yuling Chen ◽  
Timo Gaber
Keyword(s):  
Immune Response ◽  
Cancer Progression ◽  
Immune Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Adaptive Immune Response ◽  
Oxygen Availability ◽  
The Body ◽  
Low Oxygen ◽  
Adaptive Immune

Oxygen availability varies throughout the human body in health and disease. Under physiological conditions, oxygen availability drops from the lungs over the blood stream towards the different tissues into the cells and the mitochondrial cavities leading to physiological low oxygen conditions or physiological hypoxia in all organs including primary lymphoid organs. Moreover, immune cells travel throughout the body searching for damaged cells and foreign antigens facing a variety of oxygen levels. Consequently, physiological hypoxia impacts immune cell function finally controlling innate and adaptive immune response mainly by transcriptional regulation via hypoxia-inducible factors (HIFs). Under pathophysiological conditions such as found in inflammation, injury, infection, ischemia and cancer, severe hypoxia can alter immune cells leading to dysfunctional immune response finally leading to tissue damage, cancer progression and autoimmunity. Here we summarize the effects of physiological and pathophysiological hypoxia on innate and adaptive immune activity, we provide an overview on the control of immune response by cellular hypoxia-induced pathways with focus on the role of HIFs and discuss the opportunity to target hypoxia-sensitive pathways for the treatment of cancer and autoimmunity.

scholarly journals Long non-coding RNA FAM83H-AS1 acts as a potential oncogenic driver in human ovarian cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xiaolei Yuan ◽  
Ying Huang ◽  
Man Guo ◽  
Xiaowei Hu ◽  
Peiling Li
Keyword(s):  
Ovarian Cancer ◽  
Normal Control ◽  
Immune Cell ◽  
Multiple Cancer ◽  
Non Coding Rna ◽  
Incidence And Mortality ◽  
Cancer Types ◽  
Oncogenic Driver ◽  
Therapy Target ◽  
Long Non Coding Rna

Abstract Objective Ovarian cancer (OC) is one of the most aggressive women cancers with increasing incidence and mortality rates worldwide. Long non-coding RNAs (lncRNAs) could as major players in OC process. Although FAM83H antisense RNA1 (FAM83H-AS1) is demonstrated play an important roles in a many cancers, the detailed function and mechanism has not been reported in OC. Results We integrated multiple kinds of bioinformatics approaches and experiments validated method to evaluate functions of FAM83H-AS1 in OC. Some differential expressed lncRNAs were identified between OC and normal control tissues. FAM83H-AS1 was one of most differentially expressed lncRNAs and up-regulated in multiple cancer types. Specially, expression of FAM83H-AS1 was higher in OC and showed difference in diverse stages. High FAM83H-AS1 expression is associated with worse pan-cancer and OC outcomes. FAM83H-AS1-centric network including lncRNA-miRNA, lncRNA-protein and lncRNA-mRNA ceRNA network were constructed to infer the function and mechanism of FAM83H-AS1. There were two methylation sites including cg01399317 and cg20519035 located at FAM83H-AS1. The methylation level of cg01399317 was correlated with gene expression of FAM83H-AS1. The expression level of FAM83H-AS1 was correlated with infiltration level of immune cell including macrophage, neutrphil and dendritic cell in OC patients. Lastly, qRT-PCR showed that the expression of FAM83H-AS1 was higher in OC tissues than normal control tissues. Conclusion Collectively, these results indicated that FAM83H-AS1 may act as an oncogenic driver and it may be a potential therapy target in OC.

scholarly journals Long non-coding RNA FAM83H-AS1 acts as an oncogenic driver in human ovarian cancer

2020 ◽  
Author(s):  
Xiaolei Yuan ◽  
Ying Huang ◽  
Man Guo ◽  
Xiaowei Hu ◽  
Peiling Li
Keyword(s):  
Ovarian Cancer ◽  
Normal Control ◽  
Immune Cell ◽  
Multiple Cancer ◽  
Non Coding Rna ◽  
Incidence And Mortality ◽  
Cancer Types ◽  
Oncogenic Driver ◽  
Therapy Target ◽  
Long Non Coding Rna

Abstract Background Ovarian cancer (OC) is one of the most aggressive women cancers with increasing incidence and mortality rates worldwide. Long non-coding RNAs (lncRNAs) could as major players in OC process. Although FAM83H antisense RNA1 (FAM83H-AS1) is demonstrated play an important roles in a many cancers, the detailed function and mechanism has not been reported in OC. Methods We integrated multiple kinds of bioinformatics approaches and experiments validated method to evaluate functions of FAM83H-AS1 in OC. Results Some differential expressed lncRNAs were identified between OC and normal control tissues. FAM83H-AS1 was one of most differentially expressed lncRNAs and up-regulated in multiple cancer types. Specially, expression of FAM83H-AS1 was higher in OC and showed difference in diverse stages. High FAM83H-AS1 expression is associated with worse pan-cancer and OC outcomes. FAM83H-AS1-centric network including lncRNA-miRNA, lncRNA-protein and lncRNA-mRNA ceRNA network were constructed to infer the function and mechanism of FAM83H-AS1. There were two methylation sites including cg01399317 and cg20519035 located at FAM83H-AS1. The methylation level of cg01399317 was correlated with gene expression of FAM83H-AS1. The expression level of FAM83H-AS1 was correlated with infiltration level of immune cell including macrophage, neutrphil and dendritic cell in OC patients. Lastly, qRT-PCR showed that the expression of FAM83H-AS1 was higher in OC tissues than normal control tissues. Conclusions Collectively, these results indicated that FAM83H-AS1 may act as an oncogenic driver and it may be a potential therapy target in OC.

scholarly journals Cathepsin X Activity Does Not Affect NK-Target Cell Synapse but Is Rather Distributed to Cytotoxic Granules

2021 ◽  
Vol 22 (24) ◽  
pp. 13495
Author(s):  
Tanja Jakoš ◽  
Mateja Prunk ◽  
Anja Pišlar ◽  
Janko Kos
Keyword(s):  
T Cells ◽  
Cancer Progression ◽  
Cell Function ◽  
Immune Cell ◽  
Nk Cell ◽  
Tumour Progression ◽  
Cellular Immunotherapy ◽  
Target Cells ◽  
Lymphocyte Function ◽  
Cathepsin X

Cathepsin X is a lysosomal peptidase that is involved in tumour progression and represents a potential target for therapeutic interventions. In addition, it regulates important functions of immune cells and is implicated in the modulation of tumour cell–immune cell crosstalk. Selective cathepsin X inhibitors have been proposed as prospective antitumour agents to prevent cancer progression; however, their impact on the antitumour immune response has been overlooked. Previous studies indicate that the migration and adhesion of T cells and dendritic cells are affected by diminished cathepsin X activity. Meanwhile, the influence of cathepsin X inhibition on natural killer (NK) cell function has not yet been explored. Here, we examined the localization patterns of cathepsin X and the role of its inhibitors on the cytotoxicity of cell line NK-92, which is used for adoptive cellular immunotherapy in cancer patients. NK-92 cells depend on lymphocyte function-associated antigen 1 (LFA-1) to form stable immunoconjugates with target cells, providing, in this way, optimal cytotoxicity. Since LFA-1 is a substrate for cathepsin X activity in other types of cells, we hypothesized that cathepsin X could disturb the formation of NK-92 immunoconjugates. Thus, we employed cathepsin X reversible and irreversible inhibitors and evaluated their effects on the NK-92 cell interactions with target cells and on the NK-92 cell cytotoxicity. We show that cathepsin X inhibition does not impair stable conjugate formation or the lytic activity of NK-92 cells. Similarly, the conjugate formation between Jurkat T cells and target cells was not affected by cathepsin X activity. Unlike in previous migration and adhesion studies on T cells, in NK-92 cells cathepsin X was not co-localized with LFA-1 at the plasma membrane but was, rather, redistributed to the cytotoxic granules and secreted during degranulation.

scholarly journals Overexpression of miR-223 Promotes Tolerogenic Properties of Dendritic Cells Involved in Heart Transplantation Tolerance by Targeting Irak1

2021 ◽  
Vol 12 ◽  
Author(s):  
Shun Yuan ◽  
Yuanyang Chen ◽  
Min Zhang ◽  
Zhiwei Wang ◽  
Zhipeng Hu ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Heart Transplantation ◽  
Immune Cell ◽  
Transplant Rejection ◽  
Control Group ◽  
Rna Molecules ◽  
Heart Graft ◽  
Non Coding Rna ◽  
Antigen Presenting

Dendritic cells (DCs) are key mediators of transplant rejection. Numerous factors have been identified that regulate transplant immunopathology by modulating the function of DCs. Among these, microRNAs (miRNAs), small non-coding RNA molecules, have received much attention. The miRNA miR-223 is very highly expressed and tightly regulated in hematopoietic cells. It plays an important role in modulating the immune response by regulating neutrophils and macrophages, and its dysregulation contributes to multiple types of immune diseases. However, the role of miR-223 in immune rejection is unclear. Here, we observed expression of miR-223 in patients and mice who had undergone heart transplantation and found that it increased in the serum of both, and also in DCs from the spleens of recipient mice, although it was unchanged in splenic T cells. We also found that miR-223 expression decreased in lipopolysaccharide-stimulated DCs. Increasing the level of miR-223 in DCs promoted polarization of DCs toward a tolerogenic phenotype, which indicates that miR-223 can attenuate activation and maturation of DCs. MiR-223 effectively induced regulatory T cells (Tregs) by inhibiting the function of antigen-presenting DCs. In addition, we identified Irak1 as a miR-223 target gene and an essential regulator of DC maturation. In mouse allogeneic heterotopic heart transplantation models, grafts survived longer and suffered less immune cell infiltration in mice with miR-223-overexpressing immature (im)DCs. In the miR-223-overexpressing imDC recipients, T cells from spleen differentiated into Tregs, and the level of IL-10 in heart grafts was markedly higher than that in the control group. In conclusion, miR-223 regulates the function of DCs via Irak1, differentiation of T cells into Tregs, and secretion of IL-10, thereby suppressing allogeneic heart graft rejection.

scholarly journals Knockdown of Long Non-coding RNA SNGH3 by CRISPR-dCas9 Inhibits the Progression of Bladder Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Yu Cao ◽  
Qiong Hu ◽  
Ruiming Zhang ◽  
Ling Li ◽  
Mingjuan Guo ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Research Evidence ◽  
Histological Grade ◽  
Non Coding Rna ◽  
Clinical Relationship ◽  
Non Coding Rnas ◽  
Cancer Tissues ◽  
Long Non Coding Rna ◽  
Nucleolar Rna

Recent research evidence documents that lncRNAs (long non-coding RNAs lncRNAs) play a pivotal role in the tumorigenesis and development of tumors. LncRNA SNGH3 (small nucleolar RNA host gene 3) is highly expressed in numerous forms of cancer, serving as an oncogene in cancer progression. Nonetheless, the clinical relationship, along with the mechanism of SNGH3 in bladder cancer, have not been studied. Herein, the findings exhibited upregulation of SNGH3 in bladder cancer tissues, along with the cell lines. Furthermore, overexpressed SNGH3 was positively linked to the TNM stage, as well as the histological grade of bladder cancer. Moreover, the silencing of SNGH3, using CRISPR-dCas9, suppressed cell growth along with migration, but elevated bladder cancer cell apoptosis. In summary, we established that SNGH3 serves as a bladder cancer oncogene and could be employed as a prospective diagnostic marker for clinical use, and is also a therapeutic target for CRISPR-mediated gene therapy.

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