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 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.

Differential induction of mafF, mafG and mafK expression by electrophile-response-element activators

2002 ◽  
Vol 361 (2) ◽  
pp. 371-377 ◽  
Author(s):  
Julie A. MORAN ◽  
Erica L. DAHL ◽  
R. Timothy MULCAHY
Keyword(s):  
Stress Response ◽  
Cell Lines ◽  
Expression Patterns ◽  
Constitutive Expression ◽  
Response Element ◽  
Hek 293 ◽  
Physiological Processes ◽  
Absolute Requirement ◽  
Differential Induction ◽  
Phenylethyl Isothiocyanate

The three small Maf proteins, MafF, MafG and MafK, have been implicated in a number of physiological processes, including development, differentiation, haematopoiesis and stress response. Here we report the constitutive expression of mafF, mafG and mafK in six human cell lines derived from various tissues (HepG2, IMR-32, K-562, HEK-293, RD and A549). The expression patterns of mafF, mafG and mafK varied widely among cell lines. Because small Maf proteins have been implicated in electrophile response element (EpRE)-mediated stress response, the ability of three EpRE activators [pyrrolidinedithiocarbamate (PDTC), phenylethyl isothiocyanate (PEITC) and t-butylhydroquinone (tBHQ)] to induce small Maf expression was examined in detail in HepG2 cells. Both PDTC and PEITC induced mafF, mafG and mafK expression, whereas tBHQ failed to markedly induce any of the three small Mafs. Where a response was observed, mafF was induced to the greatest extent compared with mafG and mafK, and this response was transcriptionally mediated. PDTC also induced small Maf expression in the other cell lines examined, with patterns of induction varying among cell lines. The differences in expression among the cell lines examined, coupled with the induction patterns observed, indicate that the three small maf genes are stress-responsive, but may be regulated via differing mechanisms. Furthermore, the fact that tBHQ, PDTC and PEITC induce EpRE activity, but that tBHQ fails to markedly induce any of the small Mafs, suggests that up-regulation of small Mafs is not an absolute requirement for EpRE-mediated gene expression.

Prostacyclin synthase (PTGIS) expression and epigenetic regulation in non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22160-e22160
Author(s):  
S. G. Gray ◽  
M. C. Cathcart ◽  
N. Al-Sarraf ◽  
G. P. Pidgeon ◽  
K. J. O'Byrne
Keyword(s):  
Lung Cancer ◽  
Cell Lines ◽  
Epigenetic Regulation ◽  
Histone Deacetylases ◽  
Translational Regulation ◽  
Expression Patterns ◽  
Dna Methyltransferases ◽  
Variable Expression ◽  
Oncology Research ◽  
Prostacyclin Synthase

e22160 Background: Prostacyclin synthase (PTGIS) inhibits platelet aggregation and promotes vasodilation. Overexpression of this gene has been shown to inhibit lung cancer growth in a mouse model. Hypermethylation of the PTGIS promoter resulting in downregulation of PTGIS expression has been implicated in colorectal cancer. In this study we have examined both the expression patterns and epigenetic regulation of PTGIS in NSCLC. Methods: DNA/RNA and protein was extracted from matched tumour/normal samples (Thoracic Oncology Research Group BioBank, St James Hospital). PTGIS in these samples and a panel of retrospective resected lung samples was examined by immunohistochemistry and western blotting. A panel of NSCLC cell lines were treated with inhibitors to histone deacetylases (HDi) and DNA methyltransferases (DNMTi) and PTGIS expression examined by RT-PCR. Chromatin immunoprecipitation (ChIP) was used to examine changes to the PTGIS promoter in response to HDi. Results: PTGIS was found to have variable expression in both tumour samples and a panel of lung cancer cell lines. PTGIS expression was demonstrated in the vascular endothelial and bronchial epithelial cells of normal and cancerous sections. A striking variation in intratumoural PTGIS expression was observed. Methylation analysis of cell lines demonstrated hypermethylation of the PTGIS promoter. Treating cells with epigenetic inhibitors resulted in significant upregulation of PTGIS expression. Direct chromatin remodelling of the PTGIS promoter was confirmed. Conclusions: PTGIS is epigenetically regulated. The discrepancy between PTGIS mRNA and protein levels in tumor samples indicates that post-transcriptional and post-translational regulation of PTGIS is central to expression and requires further elucidation. Increased PTGIS expression is a potential therapeutic strategy for tumour prevention. [Table: see text]

scholarly journals Spontaneous changes in intermediate filament protein expression patterns in lung cancer cell lines

1988 ◽  
Vol 91 (1) ◽  
pp. 91-108
Author(s):  
J.L. Broers ◽  
M.K. Rot ◽  
T. Oostendorp ◽  
G. Bepler ◽  
L. De Leij ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Carcinoma ◽  
Cell Line ◽  
Cell Lines ◽  
Squamous Cell ◽  
Expression Patterns ◽  
Small Cell ◽  
Intermediate Filament Protein ◽  
Lung Cancer Cell ◽  
Filament Protein

The usefulness of cell lines in the study and prediction of the clinical behaviour of lung cancer is still a matter of debate. However, lung tumour cell cultures have been of value in investigations concerning molecular and cell biological aspects of these neoplasms. Especially in the examination of characteristics specific for the main types of differentiation (squamous cell carcinoma, adenocarcinoma, small cell carcinoma), in vitro studies have been most important. Twenty eight lung cancer cell lines were cultured for up to four years, and were examined at regular intervals for their intermediate filament protein (IFP) expression patterns using a panel of cytokeratin (CK) and neurofilament (NF) antibodies. These studies showed that the classic type of small cell lung cancer (SCLC) cell lines contain CKs 8, 18, and occasionally CK 19, while the variant-type SCLC cell lines generally express no CKs but can contain NFs. Non-SCLC cell lines, such as squamous cell carcinoma and adenocarcinoma cell lines, contain CKs 7 (in most cases), 8, 18 and 19. In one variant SCLC cell line and in one adenocarcinoma cell line CKs 4, 10 and 13, characteristic of squamous cell differentiation, were found. Although most cell lines have remained stable with respect to growth characteristics and IFP expression patterns, five lung cancer cultures exhibited a transition from one cell type to another, paralleled by changes in IFP expression. Progressions from classic to variant SCLC cell lines have been observed, next to conversions from variant SCLC to cell lines re-expressing cytokeratins. In some cases this resulted in a coexpression of CKs and NFs within a cell line and even within individual tumour cells. These results strongly support the earlier finding that CK expression in SCLC cell lines is a reliable marker for the classic type of differentiation, while the absence of CKs and the presence of NFs marks the variant type of differentiation. Our results are discussed in view of previous histological findings.

Differential effect of hypoxia and acidity on lung cancer cell and fibroblast metabolism

2017 ◽  
Vol 95 (3) ◽  
pp. 428-436 ◽  
Author(s):  
Alexandra Giatromanolaki ◽  
Maria Liousia ◽  
Stella Arelaki ◽  
Dimitra Kalamida ◽  
Stamatia Pouliliou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Metabolic Response ◽  
Expression Patterns ◽  
Lung Fibroblasts ◽  
Normal Lung ◽  
Lung Cancer Cell ◽  
Protein Levels

This study examined the metabolic response of lung cancer cells and normal lung fibroblasts to hypoxia and acidity. GLUT1 and HXKII mRNA/protein expression was up-regulated under hypoxia in the MRC5 fibroblasts and in the A549 and H1299 lung cancer cell lines, indicating intensified glucose absorption and glycolysis. Under hypoxia, the LDHA mRNA and LDH5 protein levels increased in the cancer cells but not in the fibroblasts. Acidity suppressed the above-mentioned hypoxia effect. PDH-kinase-1 (PDK1 mRNA and protein) and inactive phosphorylated-PDH protein levels were induced under hypoxia in the cancer cells, whereas these were reduced in the MRC5 lung fibroblasts. In human tissue sections, the prevalent expression patterns supported the contrasting metabolic behavior of cancer cells vs. tumor fibroblasts. The monocarboxylate/lactate transporter 1 (MCT1) was up-regulated in all the cell lines under hypoxic conditions, but it was suppressed under acidic conditions. The mitochondrial DNA (mtDNA) content per cell decreased significantly in the A549 cancer cell line under hypoxia, but it increased in the MRC5 fibroblasts. Taking into account these findings, we suggest that, under hypoxia, cancer cells intensify the anaerobic direction in glycolysis, while normal fibroblasts prefer to seek energy by intensifying the aerobic use of the available oxygen.

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 LINE-1 ORF1p RIP-seq reveals widespread association with p-body enriched mRNAs

2020 ◽  
Author(s):  
Erica M. Briggs ◽  
Wilson McKerrow ◽  
Paolo Mita ◽  
Jef D. Boeke ◽  
Susan K. Logan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Expression Patterns ◽  
Reverse Transcriptase Activity ◽  
The Cancer Genome Atlas ◽  
Prostate Tumors ◽  
Before And After ◽  
Copy And Paste ◽  
Androgen Independent

AbstractBackgroundLong INterspersed Element-1 (LINE-1) is an autonomous retroelement able to “copy-and-paste” itself into new loci of the host genome through a process called retrotransposition. The LINE-1 bicistronic mRNA codes for two proteins, ORF1p, a nucleic acid chaperone, and ORF2p, a protein with endonuclease and reverse transcriptase activity. Both proteins bind LINE-1 mRNA in cis and are necessary for retrotransposition. While LINE-1 transcription is usually repressed in most healthy somatic cells through a plethora of mechanisms, ORF1p expression has been observed in nearly 50% of tumors, and new LINE-1 insertions have been documented in a similar fraction of tumors, including prostate cancer.ResultsHere, we utilized RNA ImmunoPrecipitation (RIP) and the L1EM analysis software to identify ORF1p bound RNA in prostate cancer cells. We identified LINE-1 loci that were expressed in androgen sensitive and androgen independent cells, that we show are representative of LINE-1 copies expressed in prostate cancer before and after treatment. In all androgen independent cells, we found higher levels of LINE-1 RNA, as well as unique expression patterns of LINE-1 loci. Interestingly, we observed that ORF1p bound many non-LINE-1 mRNA in all prostate cancer cell lines evaluated, and polyA RNA, and RNA localized in p-bodies were especially enriched. Furthermore, the expression levels of many of the identified ORF1p bound mRNAs also correlated with expression of LINE-1 RNA in prostate tumors from The Cancer Genome Atlas (TCGA).ConclusionOur results show a significant remodeling of LINE-1 loci expression in androgen independent cell lines when compared to parental androgen dependent cells, suggesting an evolution of LINE-1 expression during prostate cancer progression. Additionally, our finding that ORF1p bound a significant amount of non-LINE-1 mRNA, and that the enriched ORF1p bound mRNAs are also amplified in LINE-1 expressing TCGA prostate tumors, suggest that ORF1p may play a role in non-LINE-1 RNA processing and regulation of specific transcripts in prostate tumors.

scholarly journals Metabolic Diversity in Human Non-Small Cell Lung Cancer Cells

2019 ◽  
Author(s):  
Pei-Hsuan Chen ◽  
Ling Cai ◽  
Kenneth Huffman ◽  
Chendong Yang ◽  
Jiyeon Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Expression Patterns ◽  
Small Cell ◽  
Metabolic Reprogramming ◽  
Small Cell Lung

SummaryIntermediary metabolism in cancer cells is regulated by diverse cell-autonomous processes including signal transduction and gene expression patterns arising from specific oncogenotypes and cell lineages. Although it is well established that metabolic reprogramming is a hallmark of cancer, we lack a full view of the diversity of metabolic programs in cancer cells and an unbiased assessment of the associations between metabolic pathway preferences and other cell-autonomous processes. Here we quantified over 100 metabolic features, mostly from 13C enrichment of molecules from central carbon metabolism, in over 80 non-small cell lung cancer (NSCLC) cell lines cultured under identical conditions. Because these cell lines were extensively annotated for oncogenotype, gene expression, protein expression and therapeutic sensitivity, the resulting database enables the user to uncover new relationships between metabolism and these orthogonal processes.

scholarly journals LINC00261 and the Adjacent Gene FOXA2 Are Epithelial Markers and Are Suppressed during Lung Cancer Tumorigenesis and Progression

2018 ◽  
Vol 5 (1) ◽  
pp. 2 ◽  
Author(s):  
Sonam Dhamija ◽  
Andrea Becker ◽  
Yogita Sharma ◽  
Ksenia Myacheva ◽  
Jeanette Seiler ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Large Scale ◽  
Patient Survival ◽  
Cancer Cell Lines ◽  
Specific Marker ◽  
Lung Cancer Cell ◽  
Mesenchymal Transition

Lung cancer continues to be the leading cause of cancer-related deaths worldwide, with little improvement in patient survival rates in the past decade. Long non-coding RNAs (lncRNAs) are gaining importance as possible biomarkers with prognostic potential. By large-scale data mining, we identified LINC00261 as a lncRNA which was significantly downregulated in lung cancer. Low expression of LINC00261 was associated with recurrence and poor patient survival in lung adenocarcinoma. Moreover, the gene pair of LINC00261 and its neighbor FOXA2 were significantly co-regulated. LINC00261 as well as FOXA2 negatively correlated with markers for epithelial-to-mesenchymal transition (EMT) and were suppressed by the EMT inducer TGFβ. Hierarchical clustering of gene expression data from lung cancer cell lines could further verify the association of high LINC00261/FOXA2 expression to an epithelial gene signature. Furthermore, higher expression of the LINC00261/FOXA2 locus was associated with lung cancer cell lines with lower migratory capacity. All these data establish LINC00261 and FOXA2 as an epithelial-specific marker pair, downregulated during EMT and lung cancer progression, and associated with lower cell migration potential in lung cancer cells.

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