<i>TERT's</i> role in colorectal carcinogenesis

Pellatt, Andrew J.; Wolff, Roger K.; Herrick, Jennifer S.; Lundgreen, Abbie; Slattery, Martha L.

doi:10.1002/mc.21885

Cited by 20 publications

(22 citation statements)

References 32 publications

(36 reference statements)

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“…Telomeres determine the genomic stability of a tumor primarily by shortening the telomere lengths in the tumor itself [38]. Previous studies showed that hTERT was a target gene of colorectal cancer [39]. In our study, we found that hTERT was highly expressed in CRC in combination with CDC5L, and the Kaplan-Meier analysis demonstrated a poor clinicopathological outcome associated with this dual expression.…”

Section: Discussionsupporting

confidence: 56%

CDC5L Promotes hTERT Expression and Colorectal Tumor Growth

Zhang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide because the survival rate remains low. Cell division cycle 5-like (CDC5L) is highly expressed in some cancer cells, but the mechanism requires clarification. Human telomerase reverse transcriptase (hTERT) plays important roles in CRC. Methods: This study aimed to identify a link between CDC5L and hTERT and to determine their effects on the signaling pathways, migration and prognosis of CRC cells. We first treated LoVo cells with biotin-labeled hTERT and identified CDC5L. Then, pulldown and ChIP assays were used to verify whether CDC5L was a promoter of hTERT. The roles of CDC5L and hTERT in cell growth and migration were studied using siRNA in vivo and in vitro. 130 human CRC specimens were analyzed using immunohistochemistry. Western blot and wound scratch analyses were used to determine the signaling pathway for CDC5L-mediated activation of CRC growth and migration. Results: We identified CDC5L as a new hTERT promoter-binding protein. Clinically, CDC5L and hTERT expression levels were key factors in the prognosis of CRC patients. CDC5L knockdown inhibited tumor growth by down-regulating hTERT expression, and CDC5L was shown to be a transcriptional activator of hTERT in a luciferase reporter assay. Conclusion: Altogether, the above results demonstrated that CDC5L was positively correlated with hTERT as a key promoter of CRC cells. To some extent, our findings suggest that CDC5L may serve as a novel therapeutic target for human colorectal cancer.

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Section: Discussionsupporting

confidence: 56%

CDC5L Promotes hTERT Expression and Colorectal Tumor Growth

Zhang

et al. 2017

Cell Physiol Biochem

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“…PubMed was searched for various combinations of ‘NSAID’, ‘aspirin’, ‘colorectal cancer’, ‘snp(s)’, ‘gene variant’ and ‘polymorphisms’ resulting in 85 abstracts (December 2013). All studies suggesting that they presented original data on polymorphisms and NSAID interaction were retrieved (46 articles) and reviewed and all studies reporting original data on interaction between polymorphisms and NSAID use in relation to risk of CRC were included (seven prospective cohort studies and 21 case–control studies). In addition, two studies were identified in the reference lists from found articles .…”

Section: Methodsmentioning

confidence: 84%

“…studies with retrospective collection of data on NSAID use (case–control studies). In total, eight prospective and 21 case–control studies were identified. Tables and S1 show results on interactions between NSAID use and polymorphisms in relation to CRC from prospective and case–control studies respectively.…”

Section: Resultsmentioning

confidence: 99%

Systematic review: interactions between aspirin, and other nonsteroidal anti‐inflammatory drugs, and polymorphisms in relation to colorectal cancer

Andersen

Vogel

2014

Aliment Pharmacol Ther

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BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) include aspirin (acetylsalicylic acid, ASA). Long-term use of NSAIDs has been associated with lowered risk of colorectal cancer (CRC), but the use is hampered by adverse effects. Also, the anti-carcinogenic effects of NSAIDs are incompletely understood. Understanding biological effects of NSAIDs may help developing new preventive medical strategies.AimTo identify gene–environment interactions between genetic variation and NSAID use in relation to risk of CRC.MethodsWe performed a PubMed literature search and all studies reporting original data on interactions between NSAIDs and polymorphisms in relation to CRC were evaluated.ResultsWe found indications that aspirin interacted with rs6983267 close to MYC (encoding a transcription factor involved in cell cycle progression, apoptosis and cellular transformation) and NSAIDs interacted with rs3024505 and rs1800872 in or close to IL10 (encoding IL-10) in preventing CRC. Homozygous carriers of the variant allele of rs6983267 (ca. 25% of the population) halved their risk for CRC by aspirin use compared to homozygous wildtype carriers who did not benefit from aspirin intake. No interaction between use of NSAIDs and PTGS-2 (encoding COX-2) in relation to CRC risk was detected. Other findings of interactions between genes in inflammatory and oncogenic pathways and NSAIDs were considered suggestive.ConclusionsKnowledge of underlying biological effects of NSAIDs in relation to CRC is scarce and the basis for stratifying the patients for preventive treatment is not yet available. Further studies assessing interactions between long-term NSAID exposure and genetic variation in relation to CRC are warranted in large well-characterised prospective cohorts.

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“…It is difficult to render the pooled analysis stratified by age groups, which were not consistently classified among these studies. Individual studies [45, 49] as well as a systematic review had suggested an interaction between aspirin or non-steroidal anti-inflammatory drug use [49, 50] and genes encoding transcription factor [49] or a combined effect of life style with gene encoding [27] in oncogenesis, inflammatory and drug metabolic pathways in relation to risk of CRC [50]. Hence, our results might be influenced by these confounding factors.…”

Section: Discussionmentioning

confidence: 96%

Association between telomere length and the risk of colorectal cancer: a meta-analysis of observational studies

et al. 2017

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BackgroundHuman chromosomes are capped and stabilized by telomeres. Telomere length regulates a ‘cellular mitotic clock’ that defines the number of cell divisions and hence, cellular life span. This study aimed to synthesize the evidence on the association between peripheral blood leucocytes (PBL) telomere length and the risk of colorectal cancer (CRC).MethodsWe searched relevant studies in electronic databases. When two or more observational studies reported the same outcome measures, we performed pooled analysis. All the analyses were performed on PBL using PCR. The odds ratio (OR) and its 95% confidence interval (CI) were used to assess the strength of association.ResultsSeven studies (with 8 datasets) were included in this meta-analysis; 3 prospective studies, 3 retrospective studies and 1 study with a separate prospective and retrospective designs. The pooled analysis of 4 prospective studies (summary OR 1.01, 95% CI: 0.77–1.34, I 2:30%) and 4 retrospective studies (summary OR 1.65, 95% CI: 0.96–2.83, I 2:96%) showed no relationship between PBL telomere length and the CRC risk. A subgroup analysis of 2 prospective studies exclusively on females also showed no association between PBL telomere length and the CRC risk (summary OR, 1.17, 95% CI:0.72–1.91, I 2:57%).ConclusionThe current analysis is insufficient to provide evidence on the relationship between PBL telomere length and the risk of CRC. Findings suggest that there may be a complex relationship between PBL telomere length and the CRC risk or discrepancy between genetics, age of patients and clinical studies. Future well powered, large prospective studies on the relationship between telomere length and the risk of CRC, and the investigations of the biologic mechanisms are recommended.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2997-3) contains supplementary material, which is available to authorized users.

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TERT's role in colorectal carcinogenesis

Cited by 20 publications

References 32 publications

CDC5L Promotes hTERT Expression and Colorectal Tumor Growth

CDC5L Promotes hTERT Expression and Colorectal Tumor Growth

Systematic review: interactions between aspirin, and other nonsteroidal anti‐inflammatory drugs, and polymorphisms in relation to colorectal cancer

Association between telomere length and the risk of colorectal cancer: a meta-analysis of observational studies

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