Expression of Cell Cycle Regulatory Proteins and Analysis of Apoptosis in Normal Nasal Mucosa and in Nasal Polyps

2005 ◽  
Vol 19 (6) ◽  
pp. 549-553 ◽  
Author(s):  
Werner Garavello ◽  
Paola Viganò ◽  
Marco Romagnoli ◽  
Lorenza Sordo ◽  
Emilio Berti ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nasal Mucosa ◽  
Nasal Polyps ◽  
Normal Mucosa ◽  
Cellular Growth ◽  
Regulatory Proteins ◽  
Biological Behavior ◽  
Proliferating Cells ◽  
Ki 67 ◽  
Sequence Of Events

Background The etiopathogenesis of nasal polyps still is to be clarified. Although hyperplasia is a typical feature of these pathological processes, little attention has been paid to specific aspects of cellular growth in polyps. We have evaluated the expression and localization of some of the regulatory proteins that direct the cell through the specific sequence of events culminating in mitosis or apoptosis in nasal polyps. Methods Twenty samples of nasal polyps and 20 samples of normal nasal mucosa have been analyzed for apoptotic index by detecting the DNA 3’ OH ends deriving from DNA fragmentation. Moreover, they have been evaluated by immunohistochemical staining for expression of Ki-67, cyclins A and B1, p53, p21, p27, murine double minute clone 2, and Bcl-2. Results We have identified a greater proportion of proliferating cells in the lining epithelial cells of the polyps when compared with the normal mucosa as stained with anti–Ki-67 antibodies. An overexpression of p53, MDM2, and Bcl-2 and an increased apoptosis were observed in nasal polyps compared with the normal mucosa, whereas no variation of p27 expression was observed. The p21 and cyclins A and B1 were rarely expressed in both pathological and normal tissue. Conclusion The p53-based control system of cell cycle progression appears to be altered in nasal polyps, potentially leading to an abrogation of the DNA damage checkpoint. Evaluation of the expression of the regulatory proteins that direct the cells throughout their cycle in nasal polyps may allow a better understanding of the biological behavior and clinical outcome of these benign pathological entities.

The murine Ki-67 cell proliferation antigen accumulates in the nucleolar and heterochromatic regions of interphase cells and at the periphery of the mitotic chromosomes in a process essential for cell cycle progression

1996 ◽  
Vol 109 (1) ◽  
pp. 143-153 ◽  
Author(s):  
M. Starborg ◽  
K. Gell ◽  
E. Brundell ◽  
C. Hoog
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Tandem Repeats ◽  
Sequence Motifs ◽  
Mitotic Chromosomes ◽  
Proliferating Cells ◽  
Ki 67 ◽  
Cycle Progression ◽  
Conserved Sequence ◽  
Interphase Cells

We have isolated the murine homologue of the human Ki-67 antigen. The Ki-67 antigen is used as a marker to assess the proliferative capacity of tumour cells; however, its cellular function is not known. The murine Ki-67 cDNA sequence (TSG126) was found to contain 13 tandem repeats, making up more than half of the total protein size. A comparison of this repetitive sequence block to its human counterpart, which contains 16 consecutive repeat units, revealed several conserved sequence motifs, including one motif frequently observed in proteins interacting with DNA. An antiserum developed against the product of the TSG126 cDNA clone identified a protein with an apparent molecular mass of 360 kDa, mainly expressed in proliferating cells. The TSG126 protein begins to accumulate during the late G1 stage of the cell cycle and is first seen as numerous small granules evenly distributed throughout the nucleus. During the S and the G2 phases, larger foci that overlap with the nucleoli and the heterochromatic regions are formed. At the onset of mitosis the TSG126 protein undergoes a dramatic redistribution process and becomes associated with the surface of the condensed chromosomes. The relative absence of the TSG126 protein from G1 interphase cells strongly argues against a model where the association of the TSG126 protein with mitotic chromosomes merely reflects a mechanism for the symmetrical distribution of nucleolar proteins between daughter cells. Instead, the intracellular distribution of the TSG126 protein during the cell cycle suggests that it could have a chromatin-associated function in both interphase and mitotic cells. Microinjection of anti-TSG126 antibodies into proliferating Swiss-3T3 fibroblasts was found to delay cell cycle progression, indicating that the TSG126 protein has an essential nuclear function.

scholarly journals The Hypothesis of the Prolonged Cell Cycle in Turner Syndrome

2021 ◽  
Author(s):  
Francisco Álvarez-Nava
Keyword(s):  
Cell Cycle ◽  
Turner Syndrome ◽  
Low Birthweight ◽  
Sex Chromosome ◽  
Heart Diseases ◽  
Cellular Growth ◽  
Proliferating Cells ◽  
Cycle Frequency ◽  
Increased Risk ◽  
New Findings

Turner syndrome (TS) is a chromosomal disorder that is caused by a missing or structurally abnormal second sex chromosome. Subjects with TS are at an increased risk of developing intrauterine growth retardation, low birthweight, short stature, congenital heart diseases, infertility, obesity, dyslipidemia, hypertension, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular diseases (stroke and myocardial infarction). The underlying pathogenetic mechanism of TS is unknown. The assumption that X chromosome-linked gene haploinsufficiency is associated with the TS phenotype is questioned since such genes have not been identified. Thus, other pathogenic mechanisms have been suggested to explain this phenotype. Morphogenesis encompasses a series of events that includes cell division, the production of migratory precursors and their progeny, differentiation, programmed cell death and integration into organs and systems. The precise control of the growth and differentiation of cells is essential for normal development. The cell cycle frequency and the number of proliferating cells are essential in cell growth. 45,X cells have a failure to proliferate at a normal rate, leading to a decreased cell number in a given tissue during organogenesis. A convergence of data indicates an association between a prolonged cell cycle and the phenotypical features in Turner syndrome. This review aims to examine old and new findings concerning the relationship between a prolonged cell cycle and TS phenotype. These studies reveal a diversity of phenotypic features in TS that could be explained by reduced cell proliferation. The implications of this hypothesis for our understanding of the TS phenotype and its pathogenesis are discussed. It is not surprising that 45,X monosomy leads to cellular growth pathway dysregulation with profound deleterious effects on both embryonic and later stages of development. The prolonged cell cycle could represent the beginning of the pathogenesis of TS, leading to a series of phenotypic consequences in embryonic/fetal, neonatal, pediatric, adolescence, and adulthood life.

scholarly journals Expression of regulatory proteins and proliferative activity in relation to phenotypic characteristics of upper urothelial carcinoma

2011 ◽  
Vol 68 (7) ◽  
pp. 567-574 ◽  
Author(s):  
Zana Dolicanin ◽  
Ljubinka Jankovic-Velickovic ◽  
Biljana Djordjevic ◽  
Milan Visnjic ◽  
Ivana Pesic ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Molecular Markers ◽  
Urothelial Carcinoma ◽  
Cyclin D1 ◽  
Regulatory Proteins ◽  
High Expression ◽  
Phenotypic Characteristics ◽  
Ki 67 ◽  
Altered Expression ◽  
Her 2

Background/Aim. Deregulation of the normal cell cycle is common in upper urothelial carcinoma (UUC). The aim of this study was to investigate the expression of regulatory proteins of the cell cycle (p53, p16, cyclin D1, HER-2) and proliferative Ki-67 activity in UUC, and to determine their interaction and influence on the phenotypic characteristics of UUC. Methods. In 44 patients with UUC, histopathological and immunohistochemical analyses (p53, p16, cyclin D1, HER-2, and Ki-67) of tumors were done. Results. Overexpression/ altered expression of p53, p16, cyclin D1 or HER-2 was detected in 20%, 57%, 64%, and 57% of tumors, respectively. Eleven (25%) UUC had a high proliferative Ki-67 index. Forty patients (91%) had at least one marker altered, while four (9%) tumors had a wild-type status. Analysis of relationship between expressions of molecular markers showed that only high expression of p53 was significantly associated with altered p16 activity (p < 0.05). High Ki-67 index was associated with the high stage (p < 0.005), solid growth (p < 0.01), high grade (p < 0.05), and multifocality p < 0.05) of UUC, while high expression of p53 was associated with the solid growth (p < 0.05). In regression models that included all molecular markers and phenotypic characteristics, only Ki-67 correlated with the growth (p < 0.0001), stage (p < 0.01), grade (p < 0.05) and multifocality (p < 0.05) of UUC; Ki-67 and HER-2 expression correlated with the lymphovascular invasion (p < 0.05). Conclusions. This investigation showed that only negative regulatory proteins of the cell cycle, p53 and p16, were significantly associated in UUC, while proliferative marker Ki-67 was in relation to the key phenotypic characteristics of UUC in the best way.

Ki-67 Labeling Index in Breast Cancer

1989 ◽  
Vol 75 (6) ◽  
pp. 557-562 ◽  
Author(s):  
Sergio Crispino ◽  
Ambrogio Brenna ◽  
Daniela Colombo ◽  
Bajardo Flores ◽  
Silvestro D'Amico ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Monoclonal Antibody ◽  
Menopausal Status ◽  
Mitotic Rate ◽  
Labeling Index ◽  
Nuclear Antigen ◽  
Proliferating Cells ◽  
Cell Cycle Kinetics ◽  
Ki 67

Measurements of cell cycle kinetics have been found to correlate with the clinical course of patients with breast cancer. However, the thymidine labeling index and more rapid methods like flow cytometry remain complicated and costly. We assessed cell proliferation of 67 breast carcinomas by an immunoperoxidase procedure using a monoclonal antibody, Ki-67, which reacts with a nuclear antigen in proliferating cells. The percentage of Ki-67 positive cells ranged from 2% to 70 %. Tumors with high mitotic rate, high nuclear grade, high histologic grade, and negative estrogen receptors had statistically higher Ki-67 labeling rates. We found no significant differences between the Ki-67 labeling rate and other clinical (age at diagnosis, menopausal status) or pathologic (necrosis, fibrosis, vascular invasion, lymphatic invasion, cellular reaction, tumor size, lymph node metastases) features assessed. These results parallel previously reported data, and confirm that this immunohistochemical staining of breast carcinoma by Ki-67 monoclonal antibody can be considered a rapid and convenient method for assessing cell cycle kinetics. However, further studies, evaluating the correlation between Ki-67 labeling rate and prognosis are needed to better define the real usefulness of this analysis in clinical practice.

scholarly journals 40 CHARACTERIZATION OF EARLY G1 CELLS AS NUCLEAR DONORS FOR SOMATIC CELL CLONING IN CATTLE

2005 ◽  
Vol 17 (2) ◽  
pp. 170
Author(s):  
A. Kasamatsu ◽  
K. Saeki ◽  
T. Tamari ◽  
K. Shirouzu ◽  
S. Taniguchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Somatic Cell ◽  
Cell Cloning ◽  
Proliferating Cells ◽  
Blastocyst Development ◽  
Ki 67 ◽  
Quiescent Cells ◽  
Reconstructed Embryos ◽  
G1 Cells

In somatic cell cloning, the cell cycle phase of the donor cells has critical impact on nuclear reprogramming and chromosomal normality of the reconstructed embryos. Recently, enhanced development to full term was obtained with embryos reconstructed with bovine fibroblasts soon after cell division (early G1 cells, Kasinathan P et al. 2001 Nat. Biotech. 19, 1176–1178; Urakawa M et al. 2004 Theriogenology 62, 714–728). In this study, to investigate the detailed cell cycle characteristics and gene expression of the early G1 cells as nuclear donors, we examined the cell proliferating and nuclear activity by detecting PCNA and Ki-67 in the cells, and the gene expression in the cells transfected with the luciferase gene. Bovine fibroblasts were transfected with chicken β-actin/firefly luciferase fusion gene (β-act/luc+), and stably transfected; cloned cells were used for cell analysis. We compared cell cycle characteristics for quiescent cells (0.4% serum for 7 days), cell doublets (early G1 cells) prepared by the “shake-off” method, and proliferating (30 to 40% confluency) cells. The presence of PCNA and Ki-67 and the incorporation of BrdU in the cells were determined by immunohistochemical analysis. The LUC+ signal (luminescence) in the cells was detected with an imaging photon counter for 10 consecutive min. Embryos reconstructed with these cells were cultured for 168 h for examination of blastocyst development. Experiments were repeated three times, and the data were analyzed with Fisher's PLSD test following ANOVA. Incorporation of BrdU was observed only in proliferating cells (24% of the cells). Neither PCNA nor Ki-67 signals were detected in the quiescent cells. PCNA was detected but Ki-67 was not detected in early G1 cells. Both PCNA and Ki-67 were detected in the proliferating cells. A strong LUC+ signal (6354 ± 673 pixels/cell) was detected in the proliferating cells, and weak signals were detected in the early G1 (2044 ± 303 pixels/cell, P < 0.05) and quiescent cells (617 ± 59 pixels/cell, P < 0.05). The rate of blastocyst development with early G1 cells was higher (45/133, 32%) than that with starved and proliferating cells (47/233, 21%, and 41/258, 14%, respectively, P < 0.05). These results indicate that early G1 cells were actively proliferating cells because of the positive PCNA signals, but their nuclei were silent because of the absence of Ki-67 signals and the weak LUC+ signals. These characteristics of the early G1 cells might enhance the development of the reconstructed embryos. This study was supported by a Grant-in-Aid for the 21st Century COE Program of the Japan MEXT, and by a grant from the Wakayama Prefecture Collaboration of Regional Entities for the Advancement of Technological Excellence of the JST.

Molecular Alterations in Oral Carcinogenesis: Significant Risk Predictors in Malignant Transformation and Tumor Progression

2007 ◽  
Vol 22 (2) ◽  
pp. 132-143 ◽  
Author(s):  
N.G. Shah ◽  
T.I. Trivedi ◽  
R.A. Tankshali ◽  
J.A. Goswami ◽  
J.S. Shah ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Progression ◽  
Early Stage ◽  
Significant Risk ◽  
Normal Mucosa ◽  
Ki 67 ◽  
Molecular Alterations ◽  
Oral Carcinogenesis ◽  
Risk Predictors ◽  
Early Stage Carcinoma

In this study an attempt was made to establish the significance of a battery of molecular alterations and thereby identify risk predictors in oral carcinogenesis. For this purpose, EGFR, Stat3, H-ras, c-myc, p53, cyclin D1, p16, Rb, Ki-67 and Bcl-2 were localized immunohistochemically in normal mucosa (n=12), hyperplasia (n=35), dysplasia (n=25), early stage carcinoma (n=65) and advanced stage carcinoma (n=70). Deregulation occurred at an early stage and the number of alterations increased with disease progression. Using multivariate logistic regression analysis, the significant risk predictor for hyperplasia from normal mucosa was Ki-67 (OR=5.75, p=0.021); the significant risk predictors for dysplasia from hyperplasia were EGFR (OR=12.96, p=0.002), Stat3 (OR=17.16, p=0.0001), p16 (OR=5.50, p=0.039) and c-myc (OR=5.99, p=0.052); the significant risk predictors for early stage carcinoma from dysplasia were p53 (OR=6.63, p=0.0001) and Rb (OR=3.81, p=0.056); and the significant risk predictors for further progression were EGFR (OR=5.50, p=0.0001), Stat3 (OR=4.49, p=0.0001), H-ras (OR=4.05, p=0.001) and c-myc (OR=2.99, p=0.015). Cyclin D1 holds a key position linking upstream signaling pathways to cell cycle regulation. Gene products of the mitogenic signaling pathway play an equally significant role as cell cycle regulatory proteins in the hyperplasia-dysplasia-early-advanced-carcinoma sequence and together may provide a reference panel of markers for use in defining premalignant lesions and predicting the risk of malignant transformation and tumor progression.

scholarly journals Deficit in Adipose Differentiation in Mesenchymal Stem Cells Derived from Chronic Rhinosinusitis Nasal Polyps Compared to Nasal Mucosal Tissue

2020 ◽  
Vol 21 (23) ◽  
pp. 9214
Author(s):  
Emanuela Chiarella ◽  
Nicola Lombardo ◽  
Nadia Lobello ◽  
Giovanna Lucia Piazzetta ◽  
Helen Linda Morrone ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Chronic Rhinosinusitis ◽  
Nasal Mucosa ◽  
Nasal Polyps ◽  
Epithelial Mesenchymal Transition ◽  
Nasal Congestion ◽  
Normal Mucosa ◽  
Molecular Response ◽  
Mesenchymal Transition

Chronic rhinosinusitis of the nasal mucosa is an inflammatory disease of paranasal sinuses, which causes rhinorrhea, nasal congestion, and hyposmia, and in some cases, it can result in the development of nasal polyposis. Nasal polyps are benign lobular-shaped growths that project in the nasal cavities; they originate from inflammation in the paranasal mucous membrane and are associated with a high expression of interleukins (IL)-4, IL-5, IL-13, and IgE. Polyps derive from the epithelial–mesenchymal transition of the nasal epithelium resulting in a nasal tissue remodeling. Nasal polyps from three patients with chronic rhinosinusitis as well as control non-polyp nasal mucosa were used to isolate and cultivate mesenchymal stem cells characterized as CD73+, CD90+, CD105+/CD14−, CD34−, and CD45−. Mesenchymal stem cells (MSCs) cultures were induced to differentiate toward adipocytes, where lipid droplets and adipocyte genes PPARγ2, ADIPO-Q, and FABP4 were observed in control non-polyp nasal mucosa-derived mesenchymal cells but were scarcely present in the cultures derived from the nasal polyps, where apoptosis was evident. The modulation of the response to adipogenic stimulus in polyps represents a change in the molecular response that controls the cascade required for differentiation as well as possible means to specifically target these cells, sparing the normal mucosa of the nasal sinuses.

scholarly journals Yap Promotes Epithelial Cell Proliferation and Epithelium-derived Innate Cytokine Expression via the NF-κb Pathway in Chronic Rhinosinusitis With Nasal Polyps

2020 ◽  
Author(s):  
Huiyi Deng ◽  
Meijiao Li ◽  
Rui. Zheng ◽  
Huijun Qiu ◽  
Tian Yuan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Epithelial Cell ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Hippo Pathway ◽  
Signalling Pathway ◽  
Epithelial Cell Proliferation ◽  
Ki 67 ◽  
Pathway Activity

Abstract Objectives: The hippo-yes-associated protein (YAP) pathway plays an important role in epithelial cell proliferation and inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the underlying mechanisms remain unclear. This study intends to investigate the role of YAP and the nuclear factor kappa-B (NF-κB) signalling pathway in nasal epithelial cell proliferation and the expression of epithelium-derived cytokines in CRSwNP.Methods: The expression levels of YAP, TEAD1, Ki-67, and NF-κB in sinonasal mucosa, primary nasal epithelial cells (NPECs), and human nasal epithelial RPMI 2650 cells were detected by RT-qPCR and immunoblotting. NPECs were cultured and treated with verteporfin (VP), a selective YAP inhibitor, YAP shRNA or BAY 11-7082, a small molecule inhibitor of NF-κB. The relationship between cell proliferation and hippo pathway activity was explored using a cell counting kit-8 (CCK-8) assay, 5(6)-carboxyfluorescein diacetate succinimidyl ester (CFSE) labelling and colony formation assay. The cell cycle and apoptosis were examined through flow cytometry (FCM) assay. The epithelium-derived cytokines including interleukin (IL-) 33, IL-25 and thymic stromal lymphopoietin(TSLP) were detected by RT-qPCR.Results: The hippo pathway effector YAP, Ki-67, p65 NF-κB, and cyclin D1were significantly increased in CRSwNP compared with control mucosa; which was accompanied by overexpression of interleukin (IL)-33, IL-25, and thymic stromal lymphopoieth (TSLP). Pharmaceutical inhibition of YAP by VP suppressed cell proliferation of RPMI 2650 cells by blocking cell cycle progression at G0/G1 without inducing obvious cell apoptosis. Furthermore, lentiviral transfection-mediated knockdown of hippo pathway activity reduced the expression of IL-33,,IL-25, TSLP as well as p65 NF-κB in RPMI 2650 cells. Downregulation of NF-κB pathway with BAY 11-7082 in NPECs could decrease the mRNA level of TSLP, IL-33 and IL-25 accordingly.Conclusions: Inhibition of hippo pathway suppressednasal epithelial cell proliferation and declined the expression of epithelium-derived cytokines IL-33 and IL-25 and TSLP expression via the NF-κB signalling pathway in NPECs.

scholarly journals The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins.

1993 ◽  
Vol 123 (3) ◽  
pp. 513-522 ◽  
Author(s):  
C Schlüter ◽  
M Duchrow ◽  
C Wohlenberg ◽  
M H Becker ◽  
G Key ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Nuclear Protein ◽  
Open Reading Frames ◽  
Growth Fraction ◽  
Proliferating Cells ◽  
Ki 67 ◽  
Nonhistone Proteins ◽  
Molecular Weights ◽  
Absolute Requirement

The antigen defined by mAb Ki-67 is a human nuclear protein the expression of which is strictly associated with cell proliferation and which is widely used in routine pathology as a "proliferation marker" to measure the growth fraction of cells in human tumors. Ki-67 detects a double band with apparent molecular weights of 395 and 345 kD in immunoblots of proteins from proliferating cells. We cloned and sequenced the full length cDNA, identified two differentially spliced isoforms of mRNA with open reading frames of 9,768 and 8,688 bp encoding for this cell proliferation-associated protein with calculated molecular weights of 358,761 D and 319,508 D, respectively. New mAbs against a bacterially expressed part and a synthetic polypeptide deduced from the isolated cDNA react with the native Ki-67 antigen, thus providing a circle of evidence that we have cloned the authentic Ki-67 antigen cDNA. The central part of the Ki-67 antigen cDNA contains a large 6,845-bp exon with 16 tandemly repeated 366-bp elements, the "Ki-67 repeats", each including a highly conserved new motif of 66 bp, the "Ki-67 motif", which encodes for the epitope detected by Ki-67. Computer analysis of the nucleic acid and the deduced amino acid sequence of the Ki-67 antigen confirmed that the cDNA encodes for a nuclear and short-lived protein without any significant homology to known sequences. Ki-67 antigen-specific antisense oligonucleotides inhibit the proliferation of IM-9 cell line cells, indicating that the Ki-67 antigen may be an absolute requirement for maintaining cell proliferation. We conclude that the Ki-67 antigen defines a new category of cell cycle-associated nuclear nonhistone proteins.

scholarly journals The minor spliceosome offers a therapeutically viable target for the treatment of a broad spectrum of cancers

2021 ◽  
Author(s):  
Karen Doggett ◽  
Kimberly J Morgan ◽  
Stephen Mieruszynski ◽  
Benjamin B Williams ◽  
Anouk M Olthof ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Broad Spectrum ◽  
Human Cancer ◽  
Tumour Burden ◽  
Proliferating Cells ◽  
Normal Tissues ◽  
Sequence Of Events ◽  
Protein Components

AbstractMinor splicing is a second splicing system required for the correct expression of ∼700 human minor intron-containing genes (MIGs). Many MIGs are expressed in vigorously proliferating cells and are frequently dysregulated in cancer including BRAF, ERK, JNK and p38. Minor splicing is carried out by the minor spliceosome which comprises several unique components, including a 65kDa protein encoded by RNPC3. We show that Rnpc3 heterozygosity reduces tumour burden in a broad spectrum of in vivo cancer settings, without harming normal tissues. Using the collective power of zebrafish, mouse and human cancer models, we reveal a sequence of events connecting Rnpc3 deficiency and impaired splicing of MIGs to DNA damage and activation of a Tp53-dependent transcriptional program that restricts tumour burden by inducing cell cycle arrest and apoptosis. Interrogation of human liver and lung cancer transcriptomes curated in TCGA revealed that the expression of many of the genes encoding protein components of the minor spliceosome is upregulated in these cancers. This is accompanied by upregulation of the expression of MIGs that are enriched in cell cycle and DNA damage pathways. These findings suggest that cancer cells can invoke mechanisms to increase the efficiency of minor splicing to support their high proliferation rates. Finally, Kaplan Meier survival analysis shows that highly expressed MIGs are frequently associated with poor patient survival. Taken together, these results indicate that the minor spliceosome offers a therapeutically viable target for the treatment of a broad spectrum of cancers.

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