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Telomerase
Telomerase telomerase(8)
Telomerase is an RT, a ribonucleoprotein that is an enzyme that adds DNA sequence repeats ("TTAGGG" in all vertebrates) to the 3' end of DNA strands in the telomere regions, at the ends of eukaryotic chromosomes. In normal circumstances, without the presence of telomerase, if a cell divides recursively, at some point all the progeny will reach their Hayflick limit, which is believed to be between 50-70 cell divisions until the cells become senescent and cell division stops.(1, 2) As a result, every time the chromosome is copied, only 100-200 nucleotides are lost, which causes no damage to the organism's DNA. When cells are approaching the Hayflick limit in cell cultures, the time to senescence can be extended by the inactivation of the tumor suppressor proteins - p53 and pRb. Cells that have been so-altered will eventually undergo crisis and the majority of the cells in the culture die. Sometimes, a cell does not stop dividing once it reaches crisis. In a typical situation, the telomeres are shortened, and the integrity of the chromosomes declines with every subsequent cell division. Exposed chromosome ends are interpreted as double-stranded breaks (DSB) in DNA; such damage is usually repaired by reattaching the broken ends together. When the cell does this due to telomere-shortening, the ends of different chromosomes can be attached together. This temporarily solves the problem of lacking telomeres; but, during anaphase of cell division, the fused chromosomes are randomly ripped apart, causing many mutations and chromosomal abnormalities. As this process continues, the cell's genome becomes unstable. Eventually, either sufficient damage will be done to the cell's chromosomes such that cell dies via apoptosis, or an additional mutation that activates telomerase will take place.(3)
Telomerase consists of two molecules each of TERT, telomerase RNA (TR or TERC), and dyskerin (DKC1).(4) TERT polypeptide folds with TERC, a non-coding RNA. TERT has a mitten structure that allows it to wrap around the chromosome to add single-stranded telomere repeats.(3)
Telomerase activation has been observed in about 90% of all human tumors.(5) Of the tumors that have not activated TERT, most have found a separate pathway to maintain telomere length termed ALT (Alternative Lengthening of Telomeres).(3) The strong association between telomerase activity and malignant tissue makes telomerase a plausible target for the diagnosis and treatment of cancer.(3, 6, 7)

Drugs/Indications
Trial Drugs/Indications
Generic Code Old Code Brand Company Indication trials
telomerase peptide vaccine GV1001 KAEL-GemVax P3: pancreatic, NSCLC; P2: HCC; P1/2: melanoma trials
imetelstat GRN163L Geron Geron P2: hepatoblastoma, rhabdomyosarcoma, Ewing's, NSCLC, BC, astrocytoma, MM; P1: lung, brain, CNS, lymphoma, solid, neuroblastoma trials
INO-1400/INO-9012 noncorporate P1: BC, PC, lung trials
Failed Drugs/Indications
Generic Code Old Code Brand Company Indication trials
GRNVAC1 Asterias Last trial started in 2007; P2: AML trials
V934/V935 Merck Last trial started in 2008; P1: NSCLC, BC, melanoma trials
telomerase vaccine noncorporate Last trial started in 2008; P3: pancreatic; P2: solid; P1/2: MM, PC; P1: brain, CNS, BC trials
News
References

1. Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Experimental cell research. 1961;25(3):585-621.

2. Siegel L. Are Telomeres the Key to Aging and Cancer? . 2013 [updated 2013; cited]; Available from: http://learn.genetics.utah.edu/content/begin/traits/telomeres.

3. Telomerase. [cited]; Available from: http://en.wikipedia.org/wiki/Telomerase.

4. Cohen SB, Graham ME, Lovrecz GO, Bache N, Robinson PJ, Reddel RR. Protein composition of catalytically active human telomerase from immortal cells. Science. 2007;315(5820):1850-3.

5. Shay J, Bacchetti S. A survey of telomerase activity in human cancer. European journal of cancer. 1997;33(5):787-91.

6. T. F. A novel molecular therapy using bioengineered adenovirus for human gastrointestinal cancer. Acta Med Okayama. 2011;65(3):151-62. PMCID: 21709712.

7. WE SJaW. Telomerase : a target for cancer therapeutics. . Cancer Cell. 2002;2:257 -65.

8. Keith WN, Bilsland A, Evans T, Glasspool RM. Telomerase-directed molecular therapeutics. Expert reviews in molecular medicine. 2002;4(10):1-25.



News
Telomerase is a ribonucleoprotein enzyme, which has a significant role in synthesizing DNA telomeric in eukaryotes. Telomere maintenance can cause to immortalization and malignant transformation of human cells and thereby telomerase activity must be scrutinized as an important factor in most tumor cells. The proliferation of cancer cells or apoptosis induction can be suppressed by telomerase inhibition using different therapeutic agents without any side effects upon normal cells. Natural substances, with anti-tumor effects, such as those derived from plants can be suitable candidates due to their capabilities in preventing some side effects and resistance of tumors with respect to most chemotherapeutic drugs. In this regards, many studies have shown that natural phytochemicals have inhibitory effects on telomerase activity through affecting its subunits and components. Therefore, the aim of this paper is to review the recent studies on these kinds of phytochemicals in terms of property and mechanism. Moreover, strategies for improving the therapeutic efficacy of plant-derived substances such as combination therapy and nanoformulation based approaches are included.
Friday, September 16, 2016 3:40 AM| Kachuri L, Amos CI, McKay JD, Johansson M, Vineis P, Bueno-de-Mesquita HB, Boutron-Ruault MC, Johansson M, Quirós JR, Sieri S, Travis RC, Weiderpass E, Le Marchand L, Henderson BE, Wilkens L, Goodman GE, Chen C, Doherty JA, Christiani DC, Wei Y, Su L, Tworoger S, Zhang X, Kraft P, Zaridze D, Field JK, Marcus MW, Davies MP, Hyde R, Caporaso NE, Landi MT, Severi G, Giles GG, Liu G, McLaughlin JR, Li Y, Xiao X, Fehringer G, Zong X, Denroche RE, Zuzarte PC, McPherson JD, Brennan P, Hung RJ|IARC Scientific Papers|Labels: telomerase, lung cancer

Fine mapping of chromosome 5p15.33 based on a targeted deep sequencing and high density genotyping identifies novel lung cancer susceptibility loci.

Carcinogenesis. 2016 Jan;37(1):96-105

Authors: Kachuri L, Amos CI, McKay JD, Johansson M, Vineis P, Bueno-de-Mesquita HB, Boutron-Ruault MC, Johansson M, Quirós JR, Sieri S, Travis RC, Weiderpass E, Le Marchand L, Henderson BE, Wilkens L, Goodman GE, Chen C, Doherty JA, Christiani DC, Wei Y, Su L, Tworoger S, Zhang X, Kraft P, Zaridze D, Field JK, Marcus MW, Davies MP, Hyde R, Caporaso NE, Landi MT, Severi G, Giles GG, Liu G, McLaughlin JR, Li Y, Xiao X, Fehringer G, Zong X, Denroche RE, Zuzarte PC, McPherson JD, Brennan P, Hung RJ

Abstract
Chromosome 5p15.33 has been identified as a lung cancer susceptibility locus, however the underlying causal mechanisms were not fully elucidated. Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a significant advance over previous research by investigating a large number of novel, rare variants, as well as their underlying mechanisms through telomere length. Variants for this fine-mapping study were identified through a targeted deep sequencing (average depth of coverage greater than 4000×) of 576 individuals. Subsequently, 4652 SNPs, including 1108 novel SNPs, were genotyped in 5164 cases and 5716 controls of European ancestry. After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.73×10(-9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = 2.64×10(-6)), rs112290073 (OR = 1.85, P = 1.27×10(-5)), rs138895564 (OR = 2.16, P = 2.06×10(-5); among young cases, OR = 3.77, P = 8.41×10(-4)). In addition, we found that rs139852726 (P = 1.44×10(-3)) was associated with telomere length in a sample of 922 healthy individuals. The gene-based SKAT-O analysis implicated TERT as the most relevant gene in the 5p15.33 region for adenocarcinoma (P = 7.84×10(-7)) and lung cancer (P = 2.37×10(-5)) risk. In this largest fine-mapping study to investigate a large number of rare and novel variants within 5p15.33, we identified novel lung and adenocarcinoma susceptibility loci with large effects and provided support for the role of telomere length as the potential underlying mechanism.

PMID: 26590902 [PubMed - in process]

Thursday, September 15, 2016 10:14 AM|P03 : Last 10 articles|Labels: telomerase, leukemia
Telomeres are the capping ends of chromosomes that protect the loss of genetic material and prevent chromosomal instability. In human tissue-specific stem/progenitor cells, telomere length (TL) is maintained by the telomerase complex, which consists of a reverse transcriptase catalytic subunit (TERT) and an RNA template (TERC). Very short telomeres and loss-of-function mutations in the TERT and TERC genes have been reported in acute myeloid leukemia, but the role of telomeres in acute promyelocytic leukemia (APL) has not been well established. We report the results for a large cohort of 187 PML/RARα-positive APL patients. No germline mutations in the TERT or TERC genes were identified. Codon 279 and 1062 TERT polymorphisms were present at a frequency similar to that in the general population. TL measured in blood or marrow mononuclear cells at diagnosis was significantly shorter in the APL patients than in healthy volunteers, and shorter telomeres at diagnosis were significantly associated with high-risk disease. For patients who achieved complete remission, the median increase in TL from diagnosis to remission (delta TL) was 2.0 kilobase (kb), and we found delta TL to be the most powerful predictor of overall survival when compared with well-established risk factors for poor outcomes in APL.
Acta Haematol 2016;136:210-218
Wednesday, September 14, 2016 4:23 PM|M. Fargnoli|JournalTOCs API - Journal of Investigative Dermatology (875 articles)|Labels: telomerase, melanoma

494 Heterogeneous mutational status of melanomas in multiple primary melanoma patients
C. Pellegrini C. Martorelli, G. Cipolloni, L. Di Nardo, A. Antonini, M. Maturo, M. Fargnoli
Journal of Investigative Dermatology, Vol. 136, No. 9 (2016) pp. S244 -
Multiple primary melanomas (MPM) develop in about 5% of sporadic melanoma patients and in up to 19% of melanoma patients with a positive family history. Many genetic alterations, including predisposing and/or somatic mutations, may contribute to the development of MPM and data on the genetic diversity of MPMs are limited. We aimed to assess the frequency and distribution of BRAF, NRAS and TERT promoter somatic mutations in subsequent melanomas of the same patient and evaluate the association of somatic alterations with germline mutational profile of MPM patients.

Wednesday, September 14, 2016 10:47 AM|Jayson Derrick|Biotech|Attachments|Labels: telomerase, MDS

Shares of Geron Corporation (NASDAQ: GERN) were trading at $2.08 Wednesday morning and are within two cents of its 52-week low of $2.06.

Investors punished the stock on Monday after the bio-pharmaceutical company announced an update from a clinical trial involving Imetelstat, a potent and specific inhibitor of telomerase that is administered by intravenous infusion.

The clinical trial was conducted by its partner, Janssen Biotech, and concluded that the study did not warrant any further investigation. The 4.7 mg/kg dose will now be ...

Full story available on Benzinga.com

Tuesday, September 13, 2016 11:38 PM|Johannes Giedl, Anja Rogler, Andreas Wild, Marc-Oliver Riener, Thomas Filbeck, Maximilian Burger, Petra Rümmele, Carolyn Hurst, Margaret Knowles, Arndt Hartmann, Ulrike Zinnall, Robert Stoehr|Journal of Cancer|Labels: telomerase, bladder cancer

Activating mutations in the core promoter of the TERT gene have been described in many different tumor entities. In vitro models showed a two- to fourfold increase in transcriptional activity of the TERT promoter through creation of a consensus binding motif for Ets/TCF transcription factors caused by these mutations. TERT core promoter mutations are the most common mutations in bladder cancer with a frequency between 55.6% and 82.8% described so far, and are independent of stage and grade. Since limited data on molecular alterations of early-onset bladder tumors exists, we assessed the frequency of TERT core promoter mutations in early-onset bladder cancer. Two cohorts of bladder tumors (early-onset patient group; n=144 (age of onset of disease ≤45 years); unselected, consecutive group; n=125) were examined for TERT core promoter mutations. After microdissection and extraction of DNA the corresponding hotspot regions in the TERT core promoter were examined by Sanger-sequencing or a SNaPshot approach. A significantly lower frequency of TERT core promoter mutations was found in tumors from the early-onset cohort compared to the consecutive cohort (57.6% vs. 84.8%, p<0.001). Among the early-onset cohort cases younger than the cohort's median age of 39 years at disease onset showed a significantly reduced number of TERT promoter mutations (31/67, 46,3%) than cases aged between 39 and 45 years (52/77, 67.5%; p=0.012). This association was not found in the consecutive cases. Mutation status was independent of tumor stage and grade. We conclude that in tumors from early-onset bladder cancer patients TERT core promoter mutations are not as frequent as in bladder tumors from consecutive cases, but seem to play an important role there as well. In patients below 39 years of age TERT core promoter mutations are a more infrequent event, suggesting different mechanisms of tumorigenesis in these young patients.

Tuesday, September 13, 2016 11:38 PM|Xu Wang, Kewei Ma, Lumei Chi, Jiuwei Cui, Lina Jin, Ji-Fan Hu, Wei Li|Journal of Cancer|Labels: telomerase, lung cancer

Genetic variants from a considerable number of susceptibility loci have been identified in association with cancer risk, but their interaction with epidemiologic factors in lung cancer remains to be defined. We sought to establish a forecasting model for identifying individuals with high-risk of lung cancer by combing gene single-nucleotide polymorphisms with epidemiologic factors. Genotyping and clinical data from 500 lung cancer cases and 500 controls were used for developing the logistic regression model. We found that lung cancer was associated with telomerase reverse transcriptase (TERT) rs2736100 single-nucleotide polymorphism. The TERT rs2736100 model was still significantly associated with lung cancer risk when combined with environmental and lifestyle factors, including lower education, lower BMI, COPD history, heavy cigarettes smoking, heavy cooking emission, and dietary factors (over-consumption of meat and deficiency in fish/shrimp, vegetables, dairy products, and soybean products). These data suggest that combining TERT SNP and epidemiologic factors may be a useful approach to discriminate high and low-risk individuals for lung cancer.

Monday, September 12, 2016 5:02 PM|Onclive Articles|Labels: telomerase, MDS
The future of imetelstat as a treatment for patients with myelodysplastic syndromes is uncertain following an update on 2 clinical trials. 
Tuesday, September 6, 2016 6:00 PM|Edith Chevret|Genes|Labels: telomerase, leukemia
Telomerase expression and telomere maintenance are critical for cell proliferation and survival, and they play important roles in development and cancer, including hematological malignancies. Transcriptional regulation of the rate-limiting subunit of human telomerase reverse transcriptase gen (hTERT) is a complex process, and unveiling the mechanisms behind its reactivation is an important step for the development of diagnostic and therapeutic applications. Here, we review the main mechanisms of telomerase activation and the associated hematologic malignancies.
Wednesday, August 31, 2016 10:05 PM|Li, F., Liu, X., Sampson, J. H., Bigner, D. D., Li, C.-Y.|Cancer Research recent issues|Labels: telomerase, brain cancer
Cancer stem-like cells (CSC) are thought to drive brain cancer, but their cellular and molecular origins remain uncertain. Here, we report the successful generation of induced CSC (iCSC) from primary human astrocytes through the expression of defined genetic factors. Combined transduction of four factors, Myc, Oct-4, p53DD, and Ras, induced efficient transformation of primary human astrocytes into malignant cells with powerful tumor-initiating capabilities. Notably, transplantation of 100 transduced cells into nude mice was sufficient for tumor formation. The cells showed unlimited self-renewal ability with robust telomerase activities. In addition, they expressed typical glioma stem-like cell markers, such as CD133, CD15, and CD90. Moreover, these cells could form spheres in culture and differentiate into neuron-like, astrocyte-like, and oligodendrocyte-like cells. Finally, they also displayed resistance to the widely used brain cancer drug temozolomide. These iCSCs could provide important tools for studies of glioma biology and therapeutics development. Cancer Res; 76(17); 5143–50. ©2016 AACR.
Monday, August 15, 2016 8:46 AM|Delespaul, L., Lesluyes, T., Perot, G., Brulard, C., lartigue, l., Baud, J., Lagarde, P., Le Guellec, S., Neuville, A., Terrier, P., Vince-Ranchere, D., Schmidt, S., Debant, A., Coindre, J.-M., Chibon, F.|Clinical Cancer Research Online First Articles|Labels: telomerase, sarcoma

Purpose:Despite various differences, non-translocation-related sarcomas (comprising UPS, LMS, MFS e.g.) are unified by their complex genetics. Extensive analysis of the tumor genome using molecular cytogenetic approaches showed many chromosomal gains, losses and translocations per cell. Genomic quantitative alterations and expression variations have been extensively studied by adapted high-throughput approaches, yet translocations still remained unscreened. We therefore analyzed 117 non-translocation-related sarcomas by RNA sequencing to identify fusion genes. Experimental Design:We performed RNA sequencing and applied a bioinformatics pipeline dedicated to detection of fusion transcripts. RT-PCR and Sanger sequencing were then applied to validate predictions and to search for recurrence and specificity. Results:Among the 6,772 predicted fusion genes, 420 were in-frame. One recurrent rearrangement, consistently involving TRIO with various partners, was identified in 5.1% of cases. TRIO translocations are either intra-chromosomal with TERT or inter-chromosomal with LINC01504 or ZNF558. Our results suggest that all translocations lead to a truncated TRIO protein either directly or indirectly by alternative splicing. TRIO rearrangement is associated with a modified transcriptomic program to immunity/inflammation, proliferation and migration and an increase in proliferation. Conclusions:TRIO fusions have been identified in four different sarcoma histotypes likely meaning that they are not related to a primary oncogenic event but rather to a secondary one implicated in tumor progression. Moreover, they appear to be specific to non-translocation-related sarcomas since no such rearrangement was identified in sarcomas with simple genetics. More cases could lead to a significant association of these fusions to a specific clinical behavior.

Thursday, July 28, 2016 6:00 PM|Çagatay Güneş|Genes|Labels: telomerase
High telomerase activity is detected in nearly all human cancers but most human cells are devoid of telomerase activity. There is well-documented evidence that reactivation of telomerase occurs during cellular transformation. In humans, tumors can rely in reactivation of telomerase or originate in a telomerase positive stem/progenitor cell, or rely in alternative lengthening of telomeres, a telomerase-independent telomere-length maintenance mechanism. In this review, we will focus on the telomerase positive tumors. In this context, the recent findings that telomerase reverse transcriptase (TERT) promoter mutations represent the most common non-coding mutations in human cancer have flared up the long-standing discussion whether cancer originates from telomerase positive stem cells or telomerase reactivation is a final step in cellular transformation. Here, we will discuss the pros and cons of both concepts in the context of telomere length-dependent and telomere length-independent functions of telomerase. Together, these observations may provoke a re-evaluation of telomere and telomerase based therapies, both in telomerase inhibition for cancer therapy and telomerase activation for tissue regeneration and anti-ageing strategies.
Wednesday, July 20, 2016 9:31 AM|Chicard, M., Boyault, S., Colmet Daage, L., Richer, W., Gentien, D., Pierron, G., Lapouble, E., Bellini, A., Clement, N., Iacono, I., Brejon, S., Carrere, M., Reyes, C., Hocking, T., Bernard, V., Peuchmaur, M., Corradini, N., Faure-Conter, C., Coze, C., Plantaz, D., Defachelles, A. S., Thebaud, E., Gambart, M., Millot, F., Valteau-Couanet, D., Michon, J., Puisieux, A., Delattre, O., Combaret, V., Schleiermacher, G.|Clinical Cancer Research Online First Articles|Labels: telomerase, brain cancer

Purpose: The tumor genomic copy number profile is of prognostic significance in neuroblastoma (NB) patients. We have studied the genomic copy number profile of cell free DNA (cfDNA) and compared this to primary tumor aCGH at diagnosis. Experimental Design:In 70 patients, cfDNA genomic copy number profiling was performed using the OncoScan® platform. The profiles were classified according to the overall pattern, including numerical chromosome alterations (NCA), segmental chromosome alterations (SCA) and MYCN amplification (MNA). Results:Interpretable and dynamic cfDNA profiles were obtained in 66/70 and 52/70 cases, respectively. An overall identical genomic profile between tumor aCGH and cfDNA was observed in 47 cases (3 NCA, 22 SCA, 22 MNA). In 1 case, cfDNA showed an additional SCA not detected by tumor aCGH. In 4/8 cases with a silent tumor aCGH profile, cfDNA analysis revealed a dynamic profile (3 SCA,1 NCA). In 14 cases cfDNA analysis did not reveal any copy number changes. A total of 378 breakpoints common to the primary tumor and cfDNA of any given patient were identified, 27 breakpoints were seen by tumor aCGH, and 54 breakpoints were seen in cfDNA only, including two cases with interstitial IGFR1 gains, and two alterations targeting TERT. Conclusions:These results demonstrate the feasibility of cfDNA copy number profiling in NB patients, with a concordance of the overall genomic profile in aCGH and cfDNA-dynamic cases of 97%, and a sensitivity of 77%, respectively. Furthermore, NB heterogeneity is highlighted, suggesting that cfDNA might reflect genetic alterations of more aggressive cell clones.

The accumulated evidence has pointed to a key role of telomerase in carcinogenesis. As a RNA-dependent DNA polymerase, telomerase synthesizes telomeric DNA at the end of linear chromosomes, and attenuates or prevents telomere erosion associated with cell divisions. By lengthening telomeres, telomerase extends cellular life-span or even induces immortalization. Consistent with its functional activity, telomerase is silent in most human normal somatic cells while active only in germ-line, stem and other highly proliferative cells. In contrast, telomerase activation widely occurs in human cancer and the enzymatic activity is detectable in up to 90% of malignancies. Recently, hotspot point mutations in the regulatory region of the telomerase reverse transcriptase (TERT) gene, encoding the core catalytic component of telomerase, was identified as a novel mechanism to activate telomerase in cancer. This review discusses the cancer-specific TERT promoter mutations and potential biological and clinical significances.
Thursday, June 30, 2016 1:53 PM|Leukemia News -- ScienceDaily|Labels: telomerase, AML
The chemotherapy treatments necessary to treat Acute Myeloid Leukemia (AML) in children can be grueling on the body, and can cause health-related complications during therapy, as well as long down the road after remission. Children receiving chemotherapy for AML receive 4 to 5 intensive chemotherapy courses, and while some children recover quickly from each course, others may take several months or more, which increases their risk for life-threatening infections.
CONCLUSIONSThe coexistence of BRAF or RAS mutations enhanced the prognostic effects of TERT promoter mutations. Furthermore, TERT promoter mutations strengthened the predictions of mortality and recurrence by the ATA and TNM staging systems, particularly for high‐risk patients with DTC. Cancer 2016. © 2016 American Cancer Society. (Source: Cancer)
Tuesday, February 9, 2016 4:00 PM|Bioorganic and Medicinal Chemistry Letters|Bioorganic and Medicinal Chemistry Letters via MedWorm.com|Comments|Labels: telomerase
Authors: Xiao X, Ni Y, Jia YM, Zheng M, Xu HF, Xu J, Liao C Abstract Eight human telomerase inhibitors (5a-5h) having the core of N-acyl-4,5-dihydropyrazole with anticancer effects were identified in this study. Biological results revealed that a few compounds had potent anticancer activities against three common tumor cell lines (SGC-7901, HepG2 and MGC-803). Among them, compound 5c, with a molecular weight of only 272.2Da, had antiproliferative activities against SGC-7901 and MGC-803 with EC50 values of 2.06±0.17 and 2.89±0.62μM, respectively, better than 5-Fluorouracil. Compound 5c inhibited the enzyme of telomerase with an IC50 value of 1.86±0.51μM, surpassing the control compound, ethidium bromide. Modeling study showed that this compound can reside in the binding pocket ...
Thursday, February 4, 2016 4:00 PM|J Cell Mol Med|MedWorm: Non-Small Cell Lung Cancer|Comments|Labels: telomerase, lung cancer
Authors: Sun Y, Yang C, Chen J, Song X, Li Z, Duan M, Li J, Hu X, Wu K, Yan G, Yang C, Liu J, Tan W, Ye M Abstract WD-repeat protein 79 (WDR79), a member of the WD-repeat protein family, acts as a scaffold protein, participating in telomerase assembly, Cajal body formation and DNA double-strand break repair. Here, we first report that WDR79 is frequently overexpressed in cell lines and tissues derived from non-small cell lung cancer (NSCLC). Knockdown of WDR79 significantly inhibited the proliferation of NSCLC cells in vitro and in vivo by inducing cell cycle arrest and apoptosis. WD-repeat protein 79 -induced cell cycle arrest at the G0/G1 phase was associated with the expression of G0/G1-related cyclins and cyclin-dependent kinase complexes. We also provide evidence that WDR79 kn...

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