scholarly journals Dysregulation of a family of short noncoding RNAs, tsRNAs, in human cancer

2016 ◽  
Vol 113 (18) ◽  
pp. 5071-5076 ◽  
Author(s):  
Yuri Pekarsky ◽  
Veronica Balatti ◽  
Alexey Palamarchuk ◽  
Lara Rizzotto ◽  
Dario Veneziano ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Rnas ◽  
Northern Blot Analysis ◽  
Human Cancer ◽  
Noncoding Rnas ◽  
Lymphocytic Leukemia ◽  
P Element ◽  
Human Leukemia ◽  
Hematopoietic Malignancies ◽  
Small Noncoding Rnas

Chronic lymphocytic leukemia (CLL) is the most common human leukemia, and transgenic mouse studies indicate that activation of the T-cell leukemia/lymphoma 1 (TCL1) oncogene is a contributing event in the pathogenesis of the aggressive form of this disease. While studying the regulation of TCL1 expression, we identified the microRNA cluster miR-4521/3676 and discovered that these two microRNAs are associated with tRNA sequences and that this region can produce two small RNAs, members of a recently identified class of small noncoding RNAs, tRNA-derived small RNAs (tsRNAs). We further proved that miR-3676 and miR-4521 are tsRNAs using Northern blot analysis. We found that, like ts-3676, ts-4521 is down-regulated and mutated in CLL. Analysis of lung cancer samples revealed that both ts-3676 and ts-4521 are down-regulated and mutated in patient tumor samples. Because tsRNAs are similar in nature to piRNAs [P-element–induced wimpy testis (Piwi)-interacting small RNAs], we investigated whether ts-3676 and ts-4521 can interact with Piwi proteins and found these two tsRNAs in complexes containing Piwi-like protein 2 (PIWIL2). To determine whether other tsRNAs are involved in cancer, we generated a custom microarray chip containing 120 tsRNAs 16 bp or more in size. Microarray hybridization experiments revealed tsRNA signatures in CLL and lung cancer, indicating that, like microRNAs, tsRNAs may have an oncogenic and/or tumor-suppressor function in hematopoietic malignancies and solid tumors. Thus, our results show that tsRNAs are dysregulated in human cancer.

scholarly journals tsRNA signatures in cancer

2017 ◽  
Vol 114 (30) ◽  
pp. 8071-8076 ◽  
Author(s):  
Veronica Balatti ◽  
Giovanni Nigita ◽  
Dario Veneziano ◽  
Alessandra Drusco ◽  
Gary S. Stein ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Small Rnas ◽  
Cell Model ◽  
Expression Patterns ◽  
Cancer Staging ◽  
Lymphocytic Leukemia ◽  
Hek 293 ◽  
Small Noncoding Rnas

Small, noncoding RNAs are short untranslated RNA molecules, some of which have been associated with cancer development. Recently we showed that a class of small RNAs generated during the maturation process of tRNAs (tRNA-derived small RNAs, hereafter “tsRNAs”) is dysregulated in cancer. Specifically, we uncovered tsRNA signatures in chronic lymphocytic leukemia and lung cancer and demonstrated that thets-4521/3676cluster (now called “ts-101” and “ts-53,” respectively),ts-46, andts-47are down-regulated in these malignancies. Furthermore, we showed that tsRNAs are similar to Piwi-interacting RNAs (piRNAs) and demonstrated thatts-101andts-53can associate with PiwiL2, a protein involved in the silencing of transposons. In this study, we extended our investigation on tsRNA signatures to samples collected from patients with colon, breast, or ovarian cancer and cell lines harboring specific oncogenic mutations and representing different stages of cancer progression. We detected tsRNA signatures in all patient samples and determined that tsRNA expression is altered upon oncogene activation and during cancer staging. In addition, we generated a knocked-out cell model forts-101andts-46in HEK-293 cells and found significant differences in gene-expression patterns, with activation of genes involved in cell survival and down-regulation of genes involved in apoptosis and chromatin structure. Finally, we overexpressedts-46andts-47in two lung cancer cell lines and performed a clonogenic assay to examine their role in cell proliferation. We observed a strong inhibition of colony formation in cells overexpressing these tsRNAs compared with untreated cells, confirming that tsRNAs affect cell growth and survival.

scholarly journals Expression of L-myc and N-myc proto-oncogenes in human leukemias and leukemia cell lines

Blood ◽  
1991 ◽  
Vol 78 (11) ◽  
pp. 3012-3020 ◽  
Author(s):  
H Hirvonen ◽  
V Hukkanen ◽  
TT Salmi ◽  
TP Makela ◽  
TT Pelliniemi ◽  
...  
Keyword(s):  
Cell Lines ◽  
Leukemia Cell ◽  
Mrna Processing ◽  
Lymphocytic Leukemia ◽  
Human Leukemia ◽  
Hematopoietic Malignancies ◽  
Cell Proliferation And Differentiation ◽  
Leukemia Cell Lines ◽  
Proliferation And Differentiation ◽  
Nuclear Phosphoproteins

Abstract The myc proto-oncogenes encode nuclear phosphoproteins, which are believed to participate in the control of cell proliferation and differentiation. Deregulated expression of c-myc has been implicated in several human hematopoietic malignancies. We have studied the expression and mRNA processing of human L-myc, N-myc, and c-myc genes in a panel of human leukemias, leukemia cell lines, and normal hematopoietic cells. L-myc mRNA was expressed in three acute myeloid leukemias (AML) studied and in several myeloid leukemia cell lines. Only low expression levels were observed in adult bone marrow and in fetal spleen and thymus. The K562 and Dami leukemia cell lines showed a unique pattern of L-myc mRNA processing, with approximately 40% of L- myc mRNA lacking exon III and intron I. N-myc was expressed in five of six AML cases studied, in one of nine acute lymphocytic leukemia (ALL) cases, and in several leukemia cell lines, while c-myc mRNA was detected in all leukemias and leukemia cell lines studied. Coexpression of all three myc genes was observed in Dami and MOLT-4 cell lines and in two AMLs, and either L-myc or N-myc was coexpressed with c-myc in several other cases. These results show that in addition to c-myc, the L-myc and N-myc genes are expressed in some human leukemias and leukemia cell lines, and suggest a lack of mutually exclusive cross- regulation of the myc genes in human leukemia cells.

scholarly journals Deciphering the tRNA-derived small RNAs: origin, development, and future

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Bowen Liu ◽  
Jinling Cao ◽  
Xiangyun Wang ◽  
Chunlei Guo ◽  
Yunxia Liu ◽  
...  
Keyword(s):  
Subcellular Localization ◽  
Small Rnas ◽  
Molecular Mechanisms ◽  
Noncoding Rnas ◽  
Transfer Rna ◽  
Action Mechanism ◽  
Chemical Modifications ◽  
Future Directions ◽  
Small Noncoding Rnas ◽  
New Biomarkers

AbstractTransfer RNA (tRNA)-derived small RNAs (tsRNAs), a novel category of small noncoding RNAs, are enzymatically cleaved from tRNAs. Previous reports have shed some light on the roles of tsRNAs in the development of human diseases. However, our knowledge about tsRNAs is still relatively lacking. In this paper, we review the biogenesis, classification, subcellular localization as well as action mechanism of tsRNAs, and discuss the association between chemical modifications of tRNAs and the production and functions of tsRNAs. Furthermore, using immunity, metabolism, and malignancy as examples, we summarize the molecular mechanisms of tsRNAs in diseases and evaluate the potential of tsRNAs as new biomarkers and therapeutic targets. At the same time, we compile and introduce several resource databases that are currently publicly available for analyzing tsRNAs. Finally, we discuss the challenges associated with research in this field and future directions.

scholarly journals Small RNA Mobility: Spread of RNA Silencing Effectors and its Effect on Developmental Processes and Stress Adaptation in Plants

2019 ◽  
Vol 20 (17) ◽  
pp. 4306 ◽  
Author(s):  
Chiara Pagliarani ◽  
Giorgio Gambino
Keyword(s):  
Small Rnas ◽  
Rna Silencing ◽  
Physiological Responses ◽  
Noncoding Rnas ◽  
Environmental Cues ◽  
Physiological Changes ◽  
Abiotic And Biotic Stresses ◽  
Biotic Stresses ◽  
Small Noncoding Rnas ◽  
Surrounding Environment

Plants are exposed every day to multiple environmental cues, and tight transcriptome reprogramming is necessary to control the balance between responses to stress and processes of plant growth. In this context, the silencing phenomena mediated by small RNAs can drive transcriptional and epigenetic regulatory modifications, in turn shaping plant development and adaptation to the surrounding environment. Mounting experimental evidence has recently pointed to small noncoding RNAs as fundamental players in molecular signalling cascades activated upon exposure to abiotic and biotic stresses. Although, in the last decade, studies on stress responsive small RNAs increased significantly in many plant species, the physiological responses triggered by these molecules in the presence of environmental stresses need to be further explored. It is noteworthy that small RNAs can move either cell-to-cell or systemically, thus acting as mobile silencing effectors within the plant. This aspect has great importance when physiological changes, as well as epigenetic regulatory marks, are inspected in light of plant environmental adaptation. In this review, we provide an overview of the categories of mobile small RNAs in plants, particularly focusing on the biological implications of non-cell autonomous RNA silencing in the stress adaptive response and epigenetic modifications.

scholarly journals The functional role of exosome microRNAs in lung cancer

2017 ◽  
Vol 12 (1) ◽  
pp. 223-227 ◽  
Author(s):  
Jia Li ◽  
Wenhuan Gong ◽  
Wenfang Zhu ◽  
Xinyu Shao ◽  
Chunxia Zhang
Keyword(s):  
Lung Cancer ◽  
Expression Patterns ◽  
Cell Communication ◽  
Noncoding Rnas ◽  
Cancer Disease ◽  
Regulate Gene Expression ◽  
Small Noncoding Rnas ◽  
Incidence And Mortality ◽  
The Status

AbstractLung cancer causes the highest incidence and mortality rates of cancer disease worldwide. Despite obvious advances in lung cancer research, a better understanding of the disease is urgently needed to improve early detection and correct diagnoses. Exosomes are released from cancer cells and modulate cell-cell communication. Exosomes transfer a wide variety of molecules including microRNAs. MicroRNAs (miRNAs) are single-stranded, small noncoding RNAs that regulate gene expression. Accumulating evidence indicates that miRNA expression patterns represent the status of physiology and disease. The focus of this review is to provide an update on the progress of miRNAs of cancer-derived exosome as potential biomarkers for lung cancer.

scholarly journals miR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic leukemia cells and exerts cooperative effects with miR-221

Blood ◽  
2009 ◽  
Vol 114 (19) ◽  
pp. 4169-4178 ◽  
Author(s):  
Ai Kotani ◽  
Daon Ha ◽  
James Hsieh ◽  
Prakash K. Rao ◽  
Diana Schotte ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Acute Lymphocytic Leukemia ◽  
Target Genes ◽  
Noncoding Rnas ◽  
Lymphocytic Leukemia ◽  
Leukemia Cells ◽  
Published Data ◽  
Fusion Genes ◽  
Cooperative Effects ◽  
Small Noncoding Rnas

Abstract MLL-AF4 acute lymphocytic leukemia (ALL) has a poor prognosis. MicroRNAs (miRNA) are small noncoding RNAs that posttranscriptionally regulate expression of target mRNAs. Our analysis of previously published data showed that expression of miR-128b and miR-221 is down-regulated in MLL-rearranged ALL relative to other types of ALL. Reexpression of these miRNAs cooperatively sensitizes 2 cultured lines of MLL-AF4 ALL cells to glucocorticoids. Target genes down-regulated by miR-128b include MLL, AF4, and both MLL-AF4 and AF4-MLL fusion genes; miR-221 down-regulates CDKN1B. These results demonstrate that down-regulation of miR-128b and miR-221 is implicated in glucocorticoid resistance and that restoration of their levels is a potentially promising therapeutic in MLL-AF4 ALL.

scholarly journals Expression of L-myc and N-myc proto-oncogenes in human leukemias and leukemia cell lines

Blood ◽  
1991 ◽  
Vol 78 (11) ◽  
pp. 3012-3020
Author(s):  
H Hirvonen ◽  
V Hukkanen ◽  
TT Salmi ◽  
TP Makela ◽  
TT Pelliniemi ◽  
...  
Keyword(s):  
Cell Lines ◽  
Leukemia Cell ◽  
Mrna Processing ◽  
Lymphocytic Leukemia ◽  
Human Leukemia ◽  
Hematopoietic Malignancies ◽  
Cell Proliferation And Differentiation ◽  
Leukemia Cell Lines ◽  
Proliferation And Differentiation ◽  
Nuclear Phosphoproteins

The myc proto-oncogenes encode nuclear phosphoproteins, which are believed to participate in the control of cell proliferation and differentiation. Deregulated expression of c-myc has been implicated in several human hematopoietic malignancies. We have studied the expression and mRNA processing of human L-myc, N-myc, and c-myc genes in a panel of human leukemias, leukemia cell lines, and normal hematopoietic cells. L-myc mRNA was expressed in three acute myeloid leukemias (AML) studied and in several myeloid leukemia cell lines. Only low expression levels were observed in adult bone marrow and in fetal spleen and thymus. The K562 and Dami leukemia cell lines showed a unique pattern of L-myc mRNA processing, with approximately 40% of L- myc mRNA lacking exon III and intron I. N-myc was expressed in five of six AML cases studied, in one of nine acute lymphocytic leukemia (ALL) cases, and in several leukemia cell lines, while c-myc mRNA was detected in all leukemias and leukemia cell lines studied. Coexpression of all three myc genes was observed in Dami and MOLT-4 cell lines and in two AMLs, and either L-myc or N-myc was coexpressed with c-myc in several other cases. These results show that in addition to c-myc, the L-myc and N-myc genes are expressed in some human leukemias and leukemia cell lines, and suggest a lack of mutually exclusive cross- regulation of the myc genes in human leukemia cells.

scholarly journals Visualization of the small RNA transcriptome using seqclusterViz

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 232 ◽  
Author(s):  
Lorena Pantano ◽  
Francisco Pantano ◽  
Eulalia Marti ◽  
Shannan Ho Sui
Keyword(s):  
Gene Regulation ◽  
Small Rna ◽  
Small Rnas ◽  
Noncoding Rnas ◽  
Model Organisms ◽  
Visualization Tool ◽  
Rna Seq ◽  
Small Noncoding Rnas ◽  
Different Types ◽  
Genomic Locations

The study of small RNAs provides us with a deeper understanding of the complexity of gene regulation within cells. Of the different types of small RNAs, the most important in mammals are miRNA, tRNA fragments and piRNAs. Using small RNA-seq analysis, we can study all small RNA types simultaneously, with the potential to detect novel small RNA types. We describe SeqclusterViz, an interactive HTML-javascript webpage for visualizing small noncoding RNAs (small RNAs) detected by Seqcluster. The SeqclusterViz tool allows users to visualize known and novel small RNA types in model or non-model organisms, and to select small RNA candidates for further validation. SeqclusterViz is divided into three panels: i) query-ready tables showing detected small RNA clusters and their genomic locations, ii) the expression profile over the precursor for all the samples together with RNA secondary structures, and iii) the mostly highly expressed sequences. Here, we show the capabilities of the visualization tool and its validation using human brain samples from patients with Parkinson’s disease.

scholarly journals Visualization of the small RNA transcriptome using seqclusterViz

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 232
Author(s):  
Lorena Pantano ◽  
Francisco Pantano ◽  
Eulalia Marti ◽  
Shannan Ho Sui
Keyword(s):  
Gene Regulation ◽  
Small Rna ◽  
Small Rnas ◽  
Noncoding Rnas ◽  
Model Organisms ◽  
Visualization Tool ◽  
Rna Seq ◽  
Small Noncoding Rnas ◽  
Different Types ◽  
Genomic Locations

The study of small RNAs provides us with a deeper understanding of the complexity of gene regulation within cells. Of the different types of small RNAs, the most important in mammals are miRNA, tRNA fragments and piRNAs. Using small RNA-seq analysis, we can study all small RNA types simultaneously, with the potential to detect novel small RNA types. We describe SeqclusterViz, an interactive HTML-javascript webpage for visualizing small noncoding RNAs (small RNAs) detected by Seqcluster. The SeqclusterViz tool allows users to visualize known and novel small RNA types in model or non-model organisms, and to select small RNA candidates for further validation. SeqclusterViz is divided into three panels: i) query-ready tables showing detected small RNA clusters and their genomic locations, ii) the expression profile over the precursor for all the samples together with RNA secondary structures, and iii) the mostly highly expressed sequences. Here, we show the capabilities of the visualization tool and its validation using human brain samples from patients with Parkinson’s disease .

scholarly journals Zebrafish xenograft model of human lung cancer for studying the function of LINC00152 in cell proliferation and invasion

2020 ◽  
Author(s):  
Wenyi Shen ◽  
Juan Pu ◽  
Jing Sun ◽  
Bing Tan ◽  
Wei Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Cultured Cells ◽  
Human Cancer ◽  
Noncoding Rnas ◽  
Xenograft Model ◽  
Long Noncoding Rnas ◽  
Proliferation And Invasion

Abstract Background: Numerous studies have shown that long noncoding RNAs play important roles in human cancer progression. Although zebrafish xenografts have recently become a novel in vivo model for human cancer research, whether such models can be used to study the function of long noncoding RNAs remains unknown. Methods: In vitro studies validated the roles of LINC00152 in the proliferation and invasion of lung cancer cells. In vivo studies of zebrafish xenografts also confirmed these roles of LINC00152. In vivo confocal imaging was used to more accurately evaluate the function of LINC00152 in cell proliferation and migration. Pharmacological experiments were further performed to study the potential ability of LINC00152 downregulation combined with an EGFR inhibitor to treat tumors in cultured cells and the zebrafish xenograft model. Results: Silencing of LINC00152 suppressed cell proliferation and invasion in SPCA1 and A549 lung cancer cell lines in vitro . In the zebrafish xenograft model, knockdown of LINC00152 reduced the proliferation and migration of lung cancer cells, as indicated by the two imaging methods at different magnifications. Moreover, the knockdown of LINC00152 enhanced the inhibition effect of afatinib for lung cancer progression in cultured cells and the zebrafish xenograft model. Conclusion: Our study reveals the oncogenic roles and potential for LINC00152 to be a target for tumor treatment in lung cancer using zebrafish xenograft models, and the findings suggest that this model could be used for functional and application studies of human long noncoding RNAs in tumor biology.

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