scholarly journals Ectopic expression of pericentric HSATII RNA results in nuclear RNA accumulation, MeCP2 recruitment, and cell division defects

Chromosoma ◽  
2021 ◽  
Vol 130 (1) ◽  
pp. 75-90
Author(s):  
Catherine C. Landers ◽  
Christina A. Rabeler ◽  
Emily K. Ferrari ◽  
Lia R. D’Alessandro ◽  
Diana D. Kang ◽  
...  
Keyword(s):  
Cell Division ◽  
Cancer Cells ◽  
Ectopic Expression ◽  
Nuclear Accumulation ◽  
Primary Fibroblast ◽  
Aberrant Expression ◽  
Normal Cells ◽  
Heterochromatin Silencing ◽  
Rna Accumulation ◽  
In Cis

AbstractWithin the pericentric regions of human chromosomes reside large arrays of tandemly repeated satellite sequences. Expression of the human pericentric satellite HSATII is prevented by extensive heterochromatin silencing in normal cells, yet in many cancer cells, HSATII RNA is aberrantly expressed and accumulates in large nuclear foci in cis. Expression and aggregation of HSATII RNA in cancer cells is concomitant with recruitment of key chromatin regulatory proteins including methyl-CpG binding protein 2 (MeCP2). While HSATII expression has been observed in a wide variety of cancer cell lines and tissues, the effect of its expression is unknown. We tested the effect of stable expression of HSATII RNA within cells that do not normally express HSATII. Ectopic HSATII expression in HeLa and primary fibroblast cells leads to focal accumulation of HSATII RNA in cis and triggers the accumulation of MeCP2 onto nuclear HSATII RNA bodies. Further, long-term expression of HSATII RNA leads to cell division defects including lagging chromosomes, chromatin bridges, and other chromatin defects. Thus, expression of HSATII RNA in normal cells phenocopies its nuclear accumulation in cancer cells and allows for the characterization of the cellular events triggered by aberrant expression of pericentric satellite RNA.

scholarly journals Ectopic expression of pericentric HSATII RNA results in nuclear RNA accumulation, MeCP2 recruitment, and cell division defects

2020 ◽  
Author(s):  
Catherine C. Landers ◽  
Christina A. Rabeler ◽  
Emily K. Ferrari ◽  
Lia R. D’Alessandro ◽  
Diana D. Kang ◽  
...  
Keyword(s):  
Cell Division ◽  
Cancer Cells ◽  
Ectopic Expression ◽  
Nuclear Accumulation ◽  
Primary Fibroblast ◽  
Aberrant Expression ◽  
Normal Cells ◽  
Heterochromatin Silencing ◽  
Rna Accumulation ◽  
In Cis

AbstractWithin the pericentric regions of human chromosomes reside large arrays of tandemly repeated satellite sequences. Expression of the human pericentric satellite HSATII is prevented by extensive heterochromatin silencing in normal cells, yet in many cancer cells, HSATII RNA is aberrantly expressed and accumulates in large nuclear foci in cis. Expression and aggregation of HSATII RNA in cancer cells is concomitant with recruitment of key chromatin regulatory proteins including methyl-CpG binding protein 2 (MeCP2). While HSATII expression has been observed in a wide variety of cancer cell lines and tissues, the effect of its expression is unknown. We tested the effect of stable expression of HSATII RNA within cells that do not normally express HSATII. Ectopic HSATII expression in HeLa and primary fibroblast cells leads to focal accumulation of HSATII RNA in cis and triggers the accumulation of MeCP2 onto nuclear HSATII RNA bodies. Further, long-term expression of HSATII RNA leads to cell division defects including lagging chromosomes, chromatin bridges, and other chromatin defects. Thus, expression of HSATII RNA in normal cells phenocopies its nuclear accumulation in cancer cells and allows for the characterization of the cellular events triggered by aberrant expression of pericentric satellite RNA.

Krüppel-like factor 4 represses transcription of the survivin gene in esophageal cancer cell lines

2009 ◽  
Vol 390 (5/6) ◽  
Author(s):  
Guo Zhang ◽  
Hongxia Zhu ◽  
Yihua Wang ◽  
Shangbin Yang ◽  
Mei Liu ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Binding Sites ◽  
Ectopic Expression ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Mobility Shift ◽  
Aberrant Expression ◽  
Survivin Gene ◽  
Survivin Promoter

Abstract Aberrant expression of survivin has been shown to be regulated at the transcription level in cancer cells. In this study, we demonstrate that there are six putative binding sites of Krüppel-like factor 4 (KLF4) within the 2000-bp region upstream of the transcription start site of the human survivin gene. Luciferase reporter gene assays revealed that survivin promoter activity is repressed upon overexpression of KLF4 in EC9706 cells. A chromatin immunoprecipitation assay indicated that KLF4 indeed binds the survivin promoter in vivo. It specifically binds the site located at position -40 among the six binding sites as determined by electrophoretic mobility shift assay. Ectopic expression of KLF4 decreases the mRNA and protein levels of survivin. Furthermore, overexpression of survivin partially reverses KLF4-induced cell apoptosis. These results indicate that KLF4 is a transcriptional repressor of the human survivin gene in esophageal squamous cancer cells.

scholarly journals IDENTIFIKASI PERUBAHAN STRUKTUR DNA TERHADAP PEMBENTUKAN SEL KANKER MENGGUNAKAN DEKOMPOSISI GRAF

2017 ◽  
Vol 17 (2) ◽  
pp. 153
Author(s):  
Rondo V.S.A Morihito ◽  
Stephanie E Chungdinata ◽  
Timboeleng A Nazareth ◽  
M Iqbal Pulukadang ◽  
Roy A.M Makalew ◽  
...  
Keyword(s):  
Cell Division ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Control Cell ◽  
Hamilton Cycle ◽  
Graph Decomposition ◽  
Cancer Cell Growth ◽  
Normal Cells ◽  
Dna Structures ◽  
Control Cell Division

IDENTIFIKASI PERUBAHAN STRUKTUR DNA TERHADAP PEMBENTUKAN  SEL KANKER MENGGUNAKAN DEKOMPOSISI GRAFABSTRAKKerusakan DNA adalah salah satu penyebab yang dapat mebuat sel normal bertumbuh menjadi sel kanker. Hal ini dikarenakan DNA yang rusak dapat menyebabkan mutasi di gen vital yang mengontrol pembelahan sel sampai terjadi pembelahan sel yang tidak terkendali dan memicu pertumbuhan sel kanker. Beberapa mutasi dibutuhkan untuk mengubah sel normal menjadi sel kanker. Dalam hal ini, teori dekomposisi graf digunakan untuk menganalisa proses terjadinya pertumbuhan sel kanker yang dimulai dari kerusakan DNA yang menyebabkan terjadinya mutasi gen. Dengan teori dekomposisi graf, sebuah graf bisa difaktorkan ke dalam beberapa subgraf. Pemfaktoran ini dapat digunakan untuk melihat pola perubahan hubungan antar objek. Tujuan dari penelitian ini untuk mengidentifikasi struktur DNA terhadap pembentukan sek kanker dengan menggunakan dekomposisi graf. Yang  diidenfikasi adalah mutasi delesi, addisi, dan substitusi dimana dari mutasi-mutasi ini dilihat hasil dekomposisi graf dan apakah dari ketiga mutasi ini dapat membentuk sel kanker.Kata Kunci : Struktur DNA, Sel Kanker, Dekomposisi Graf, Perfect Matching, Hamilton cycle IDENTIFICATION OF CHANGES OF DNA STRUCTURES ON CANCER CELL FORM USING GRAPH DECOMPOSITIONABSTRACTDNA damage is one of the causes that can make normal cells grow into cancer cells. This is because damaged DNA can cause mutations in vital genes that control cell division until uncontrolled cell division and trigger the growth of cancer cells. Some mutations are needed to convert normal cells into cancer cells. In this case theory of graph decomposition will be used to analyze the process of cancer cell growth that starts from the DNA damage that causes gene mutation. With the graph decomposition theory, a graph can be factored into several subgraphs. This factoring can be used to see patterns of relationship changes between objects. The purpose of this study was to identify the structure of DNA against the formation of cancer cells by using decomposition graph. What will be identified are the deletion mutations, additions, and substitutions from which these mutations are seen in the decomposition of the graph and whether these three mutations can form cancer cells.Keywords :  Structure of DNA, Cancer Sel, Dekomposition Graph, Perfect Maching, Hamilton cycle

Depletion of death-associated protein-3 induces chemoresistance in gastric cancer cells through the β-catenin/LGR5/Bcl-2 axis

2019 ◽  
Vol 67 (5) ◽  
pp. 856-861 ◽  
Author(s):  
Yongning Jia ◽  
Ziyu Li ◽  
Xiaojing Cheng ◽  
Xiaojiang Wu ◽  
Fei Pang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Ectopic Expression ◽  
Nuclear Accumulation ◽  
Apoptosis Resistance ◽  
Gastric Cancer Cells ◽  
Downstream Target ◽  
Novel Strategy ◽  
Induced Apoptosis

Previously, we demonstrated that death-associated protein-3 (DAP3) loss drives chemoresistance in gastric cancer cells. In the present study, we aimed to determine the underlying molecular mechanism. The effect of DAP3 silencing on β-catenin signaling was assessed. The direct mediator of DAP3 silencing-induced chemoresistance was identified. Depletion of DAP3 stimulates nuclear accumulation of β-catenin and enhances β-catenin-dependent transcriptional activity in gastric cancer cells. However, the protein kinase B , , extracellular regulated protein kinase and signal transducer and activator of transcription 3 signaling pathways remain unaffected by DAP3 loss. We found that the downstream target gene LGR5 (leucine-rich G-protein coupled receptor 5) is upregulated in DAP3-depleted gastric cancer cells. Moreover, knockdown of LGR5 resensitizes DAP3-depleted gastric cancer cells to 5-fluorouracil (5-FU) and oxaliplatin. We also observed that ectopic expression of LGR5 reduces apoptosis in gastric cancer cells on treatment with 5-FU and oxaliplatin, which is accompanied by prevention of caspase-3 cleavage. The antiapoptotic protein Bcl-2 is identified as a key mediator of LGR5-induced apoptosis resistance in gastric cancer cells. The present findings indicate that DAP3 deficiency-induced chemoresistance in gastric cancer is at least partially mediated through the β-catenin/LGR5/Bcl-2 axis. Targeting LGR5 may provide a novel strategy to overcome chemoresistance in DAP3-deficient gastric cancer cells.

scholarly journals Targeting survivin in leukemia

2011 ◽  
pp. 195-204
Author(s):  
Bing Z. Carter ◽  
Michael Andreeff
Keyword(s):  
Cell Division ◽  
Cancer Cells ◽  
Poor Prognosis ◽  
Clinical Implications ◽  
Malignant Cells ◽  
Aberrant Expression ◽  
Growth And Survival ◽  
Inhibitors Of Apoptosis ◽  
Hematopoietic Malignancies ◽  
Promising Target

Survivin, a member of the inhibitors of apoptosis family of proteins, is one of the most frequently upregulated transcripts in solid tumors and hematopoietic malignancies. Survivin’s importance in tumorigenesis is attributed to the fact that it has two functions: to suppress apoptosis and to regulate cell division. The combination of these two functions gives a significant growth and survival advantage on neoplastic cells. This, together with its overexpression in cancer cells, its association with resistance to chemo- and other therapies, and the resulting poor prognosis observed in certain tumors makes survivin a promising target for therapy. In this review, we describe what is currently know about survivin regulation in normal and malignant cells, focusing in particular on the aberrant expression of the protein in leukemia and its possible clinical implications. Various strategies to target survivin will also be described.

scholarly journals Heterogeneous Nuclear Ribonucleoproteins A1 and A2 Function in Telomerase-Dependent Maintenance of Telomeres

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 334 ◽  
Author(s):  
Tong-Hong Wang ◽  
Chin-Chuan Chen ◽  
Yuan-Chao Hsiao ◽  
Yu-Han Lin ◽  
Wen-Chieh Pi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cells ◽  
Molecular Basis ◽  
Ectopic Expression ◽  
Hnrnp A1 ◽  
Proliferation Inhibition ◽  
Normal Cells ◽  
Dna Damage Responses ◽  
Heterogeneous Nuclear Ribonucleoproteins ◽  
Inhibit Cell Proliferation

The A/B subfamily of heterogeneous nuclear ribonucleoproteins (hnRNPs A/B), which includes hnRNP A1, A2/B1, and A3, plays an important role in cell proliferation. The simultaneous suppression of hnRNP A1/A2, but not the suppression of hnRNP A1 or A2 alone, has been shown to inhibit cell proliferation and induce apoptosis in cancer cells, but not in mortal normal cells. However, the molecular basis for such a differential inhibition of cell proliferation remains unknown. Here, we show that the simultaneous suppression of hnRNP A1 and hnRNP A2 resulted in dysfunctional telomeres and induced DNA damage responses in cancer cells. The inhibition of apoptosis did not alleviate the inhibition of cell proliferation nor the formation of dysfunctional telomeres in cancer cells depleted of hnRNP A1/A2. Moreover, while proliferation of mortal normal fibroblasts was not sensitive to the depletion of hnRNP A1/A2, the ectopic expression of hTERT in normal fibroblasts rendered these cells sensitive to proliferation inhibition, which was associated with the production of dysfunctional telomeres. Our study demonstrates that hnRNP A1 and A2 function to maintain telomeres in telomerase-expressing cells only, suggesting that the maintenance of functional telomeres in telomerase-expressing cancer cells employs factors that differ from those used in the telomerase-negative normal cells.

Molecular Studies on Novel Antitumor Bis 1,4-Dihydropyridine Derivatives Against Lung Carcinoma and their Limited Side Effects on Normal Melanocytes

2019 ◽  
Vol 18 (15) ◽  
pp. 2156-2168 ◽  
Author(s):  
Magda F. Mohamed ◽  
Nada S. Ibrahim ◽  
Ahmed H.M. Elwahy ◽  
Ismail A. Abdelhamid
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Cancer Cells ◽  
Cell Line ◽  
Lung Carcinoma ◽  
Carcinoma Cell ◽  
Normal Cells ◽  
Lung Carcinoma Cell Line ◽  
Molecular Studies ◽  
Dihydropyridine Derivatives

Background: Cancer is a complex genetic disease which is characterized by an abnormal cell growth, invasion and spreading to other parts of the body. There are several factors that lead to cancer by causing DNA damage and the impairment of its repair. Treatment of cancer using the chemotherapeutic drugs have adverse side effects such as toxicity as they lose their specificity toward cancer cells and affect also normal cells. Moreover, the cancer cells can resist the chemotherapeutic agents and make them ineffective. For these reasons, much attentions have been paid to develop new drugs with limited side effects on normal cells and to diminish cancer resistance to drug chemotherapy. Recently, some 1,4-dihydropyridine derivatives were reported to act as Multi-Drug Resistance (MDR) modulators that inhibit p-glycoprotein which is responsible for the inability of drugs to enter the cancer cells. Also 1,4-DHPs have antimutagenic properties against chemicals via modulating DNA repair when studied on drosophila. Objective: The objective of this study is the synthesis of bis 1,4-DHPs incorporating ester as well as ether linkages and evaluate the anticancer activity of new compounds for synergistic purpose. Different genetic tools were used in an attempt to know the mechanism of action of this compound against lung cancer. Method: An efficient one pot synthesis of bis 1,4-DHPs using 3-aminocrotononitrile and bis(aldehydes) has been developed. The cytotoxic effect against human cell lines MCF7, and A549 cell lines was evaluated. Results: All compounds exhibited better cytotoxicity toward lung carcinoma cells than breast cancer cells. With respect to lung carcinoma cell line (A549), compound 10 was the most active compound and the three other compounds 7, 8, and 9 showed comparable IC50 values. In case of breast cancer cell line (MCF7), the most active one was compound 7, while compound 8 recorded the least activity. Conclusion: we have developed an efficient method for the synthesis of novel bis 1,4-dihydropyridine derivatives incorporating ester or ether linkage. All compounds showed better cytotoxicity results against A549 than MCF7, so that lung carcinoma cell line was chosen to perform the molecular studies on it. The results showed that all compounds (7, 8, 9 and 10) caused cell cycle arrest at G1 phase. The molecular docking study on CDK2 confirmed the results of cell cycle assay which showed good binding energy between the compounds and the active site of enzyme indicating the inhibition of the enzyme.

scholarly journals Normal cells repel WWOX-negative or -dysfunctional cancer cells via WWOX cell surface epitope 286-299

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yu-An Chen ◽  
Yong-Da Sie ◽  
Tsung-Yun Liu ◽  
Hsiang-Ling Kuo ◽  
Pei-Yi Chou ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cancer Cells ◽  
Room Temperature ◽  
Metastatic Cancer ◽  
Normal Cells ◽  
Tgfβ Receptor ◽  
Membrane Type ◽  
Cell Invasiveness ◽  
And Control ◽  
Metastatic Cancer Cells

AbstractMetastatic cancer cells are frequently deficient in WWOX protein or express dysfunctional WWOX (designated WWOXd). Here, we determined that functional WWOX-expressing (WWOXf) cells migrate collectively and expel the individually migrating WWOXd cells. For return, WWOXd cells induces apoptosis of WWOXf cells from a remote distance. Survival of WWOXd from the cell-to-cell encounter is due to activation of the survival IκBα/ERK/WWOX signaling. Mechanistically, cell surface epitope WWOX286-299 (repl) in WWOXf repels the invading WWOXd to undergo retrograde migration. However, when epitope WWOX7-21 (gre) is exposed, WWOXf greets WWOXd to migrate forward for merge. WWOX binds membrane type II TGFβ receptor (TβRII), and TβRII IgG-pretreated WWOXf greet WWOXd to migrate forward and merge with each other. In contrast, TβRII IgG-pretreated WWOXd loses recognition by WWOXf, and WWOXf mediates apoptosis of WWOXd. The observatons suggest that normal cells can be activated to attack metastatic cancer cells. WWOXd cells are less efficient in generating Ca2+ influx and undergo non-apoptotic explosion in response to UV irradiation in room temperature. WWOXf cells exhibit bubbling cell death and Ca2+ influx effectively caused by UV or apoptotic stress. Together, membrane WWOX/TβRII complex is needed for cell-to-cell recognition, maintaining the efficacy of Ca2+ influx, and control of cell invasiveness.

scholarly journals CircPVT1 attenuates negative regulation of NRAS by let-7 and drives cancer cells towards oncogenicity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joshua Miguel C. Danac ◽  
Reynaldo L. Garcia
Keyword(s):  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Circular Rnas ◽  
Aberrant Expression ◽  
Mesenchymal Transition ◽  
Relative Contribution ◽  
Colorectal Cancer Cells ◽  
Migration Resistance ◽  
Global Action ◽  
A549 Lung

AbstractCircular RNAs have emerged as functional regulatory molecules whose aberrant expression has been linked to diverse pathophysiological processes. Here, we report that circPVT1 interferes with let-7 binding to NRAS, confirming this axis as one route by which circPVT1 can instigate an oncogenic program in A549 lung cancer cells and HCT116 colorectal cancer cells. CircPVT1 knockdown significantly reduced NRAS levels and attenuated cancer hallmark phenotypes such as proliferation, migration, resistance to apoptosis, cytoskeletal disorganization, and epithelial-mesenchymal transition. The effects of circPVT1 knockdown were at least partially rescued by blocking binding of let-7 to NRAS 3′UTR with a target protector, suggesting that a circPVT1/let-7/NRAS axis exists and acts in cells to reverse NRAS downregulation and favor oncogenicity. While the phenotypic effects of circPVT1 knockdown may be attributable to the global action of circPVT1, the target protection assays resolved the relative contribution of the circPVT1/let-7/NRAS axis specifically.

scholarly journals Quantum Dots as a Good Carriers of Unsymmetrical Bisacridines for Modulating Cellular Uptake and the Biological Response in Lung and Colon Cancer Cells

Nanomaterials ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 462 ◽  
Author(s):  
Joanna Pilch ◽  
Patrycja Kowalik ◽  
Piotr Bujak ◽  
Anna M. Nowicka ◽  
Ewa Augustin
Keyword(s):  
Quantum Dots ◽  
Cancer Cells ◽  
Cellular Uptake ◽  
Laser Scanning ◽  
Biological Response ◽  
Drug Carriers ◽  
Confocal Laser ◽  
Normal Cells ◽  
H460 Cells ◽  
Hct116 Cells

Nanotechnology-based drug delivery provides a promising area for improving the efficacy of cancer treatments. Therefore, we investigate the potential of using quantum dots (QDs) as drug carriers for antitumor unsymmetrical bisacridine derivatives (UAs) to cancer cells. We examine the influence of QD–UA hybrids on the cellular uptake, internalization (Confocal Laser Scanning Microscope), and the biological response (flow cytometry and light microscopy) in lung H460 and colon HCT116 cancer cells. We show the time-dependent cellular uptake of QD–UA hybrids, which were more efficiently retained inside the cells compared to UAs alone, especially in H460 cells, which could be due to multiple endocytosis pathways. In contrast, in HCT116 cells, the hybrids were taken up only by one endocytosis mechanism. Both UAs and their hybrids induced apoptosis in H460 and HCT116 cells (to a greater extent in H460). Cells which did not die underwent senescence more efficiently following QDs–UAs treatment, compared to UAs alone. Cellular senescence was not observed in HCT116 cells following treatment with both UAs and their hybrids. Importantly, QDgreen/red themselves did not provoke toxic responses in cancer or normal cells. In conclusion, QDs are good candidates for targeted UA delivery carriers to cancer cells while protecting normal cells from toxic drug activities.

Sign in / Sign up

Export Citation Format

Share Document