Drug Response Associated With and Prognostic lncRNAs Mediated by DNA Methylation and Transcription Factors in Colon Cancer

Zhang, Jiayu; Shen, Zhen; Song, Zheyu; Luan, Jian; Li, Yezhou; Zhao, Tong

doi:10.3389/fgene.2020.554833

Cited by 3 publications

(4 citation statements)

References 65 publications

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“…In a report by Zhang et al [18], LINC00460 showed significant hypomethylation in colorectal cancer tissue samples in comparison with adjacent noncancerous tissue specimens, which had a negative correlation with its expression. In addition, treatment with 5-aza-2'-deoxycytidine resulted in LINC00460 overexpression and demethylation in LOVO and SW620 cells, demonstrating that LINC00460 could be activated by DNA methylation.…”

Section: Regulation Of Linc00460 In Cancermentioning

confidence: 91%

“…LINC00460 is generally upregulated in multiple tumor cells in comparison to that in control cells (Table 1), including bladder [13,14], breast [15], cervical [16,17], colon [18,19], colorectal [10,[20][21][22][23][24], esophageal [25], gastric [26,27], ovarian [28], lung [11,[29][30][31], pancreatic [32] and papillary thyroid cancers [33][34][35], as well as acute myeloid leukemia (AML) [36], glioma [37], head and neck squamous cell carcinoma (HNSCC) [38][39][40][41][42], hepatocellular carcinoma [43][44][45], laryngeal squamous cell carcinoma [46], meningioma [47], nasopharyngeal carcinoma [48] and osteosarcoma [49]. In addition, LINC00460 is also overexpressed in these tumor tissues compared with adjacent normal tissues.…”

Section: Linc00460 Expression In Malignanciesmentioning

confidence: 99%

“…LINC00460 has been demonstrated to be involved in chemoresistance. Zhang et al [18] investigated the associations of lncRNAs and antitumor drug response, and demonstrated that LINC00460 could distinguish responses to AZD6244 and PD-0325901 in colon cancer samples. Meng and colleagues [64] demonstrated that LINC00460 is upregulated in colorectal cancer cells with oxaliplatin resistance and p53 mutations, compared with parental oxaliplatin-sensitive cells.…”

Section: Linc00460 In Chemotherapeutic or Radiation Resistancementioning

confidence: 99%

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Oncogenic roles of the lncRNA LINC00460 in human cancers

Tang

Yang

et al. 2022

Cancer Cell Int

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Long noncoding RNAs (lncRNAs) represent an important group of endogenous RNAs with limit protein-encoding capability, with a length of more than 200 nucleotides. Emerging evidence have demonstrated that lncRNAs are greatly involved in multiple cancers by playing critical roles in tumor initiation and progression. Long intergenic non-protein coding RNA 460 (LINC00460), a novel cancer-related lncRNA, exhibits abnormal expression and oncogenic function in multiple cancers, and positively correlates with poor clinical characteristics of cancer patients. LINC00460 has also been shown to be a promising biomarker for diagnosis as well as prognostic evaluation in cancer patients. In this review, we briefly summarized recent knowledge on the expression, functional roles, molecular mechanisms, and diagnostic and prognostic values of LINC00460 in human malignancies.

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Section: Regulation Of Linc00460 In Cancermentioning

confidence: 91%

Section: Linc00460 Expression In Malignanciesmentioning

confidence: 99%

Section: Linc00460 In Chemotherapeutic or Radiation Resistancementioning

confidence: 99%

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Oncogenic roles of the lncRNA LINC00460 in human cancers

Tang

Yang

et al. 2022

Cancer Cell Int

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“…16 Analysis of genome-wide, sitespecific methylation data has helped elucidate much about cancer, especially about carcinogenesis, 17,18 molecular characterization, [19][20][21] and molecular indicators of prognosis, [21][22][23] but so far, methylation studies on cancer drug efficacy have been limited in scope, for example, focusing on a single cancer. 24,25 As of yet, there have been no systematic efforts to identify drug-methylation interactions in most cancers despite mounting evidence that methylation often plays a key role in the development of cancer drug resistance. [26][27][28] The Cancer Genome Atlas (TCGA) has collected tumor samples from a wide range of cancers for molecular characterization.…”

Section: Introductionmentioning

confidence: 99%

Methylation of CpG Sites as Biomarkers Predictive of Drug-Specific Patient Survival in Cancer

2022

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Background: Though the development of targeted cancer drugs continues to accelerate, doctors still lack reliable methods for predicting patient response to standard-of-care therapies for most cancers. DNA methylation has been implicated in tumor drug response and is a promising source of predictive biomarkers of drug efficacy, yet the relationship between drug efficacy and DNA methylation remains largely unexplored. Method: In this analysis, we performed log-rank survival analyses on patients grouped by cancer and drug exposure to find CpG sites where binary methylation status is associated with differential survival in patients treated with a specific drug but not in patients with the same cancer who were not exposed to that drug. We also clustered these drug-specific CpG sites based on co-methylation among patients to identify broader methylation patterns that may be related to drug efficacy, which we investigated for transcription factor binding site enrichment using gene set enrichment analysis. Results: We identified CpG sites that were drug-specific predictors of survival in 38 cancer-drug patient groups across 15 cancers and 20 drugs. These included 11 CpG sites with similar drug-specific survival effects in multiple cancers. We also identified 76 clusters of CpG sites with stronger associations with patient drug response, many of which contained CpG sites in gene promoters containing transcription factor binding sites. Conclusion: These findings are promising biomarkers of drug response for a variety of drugs and contribute to our understanding of drug-methylation interactions in cancer. Investigation and validation of these results could lead to the development of targeted co-therapies aimed at manipulating methylation in order to improve efficacy of commonly used therapies and could improve patient survival and quality of life by furthering the effort toward drug response prediction.

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Identifying and characterizing drug sensitivity-related lncRNA-TF-gene regulatory triplets

et al. 2022

Briefings in Bioinformatics

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Recently, many studies have shown that lncRNA can mediate the regulation of TF-gene in drug sensitivity. However, there is still a lack of systematic identification of lncRNA-TF-gene regulatory triplets for drug sensitivity. In this study, we propose a novel analytic approach to systematically identify the lncRNA-TF-gene regulatory triplets related to the drug sensitivity by integrating transcriptome data and drug sensitivity data. Totally, 1570 drug sensitivity-related lncRNA-TF-gene triplets were identified, and 16 307 relationships were formed between drugs and triplets. Then, a comprehensive characterization was performed. Drug sensitivity-related triplets affect a variety of biological functions including drug response-related pathways. Phenotypic similarity analysis showed that the drugs with many shared triplets had high similarity in their two-dimensional structures and indications. In addition, Network analysis revealed the diverse regulation mechanism of lncRNAs in different drugs. Also, survival analysis indicated that lncRNA-TF-gene triplets related to the drug sensitivity could be candidate prognostic biomarkers for clinical applications. Next, using the random walk algorithm, the results of which we screen therapeutic drugs for patients across three cancer types showed high accuracy in the drug-cell line heterogeneity network based on the identified triplets. Besides, we developed a user-friendly web interface-DrugSETs (http://bio-bigdata.hrbmu.edu.cn/DrugSETs/) available to explore 1570 lncRNA-TF-gene triplets relevant with 282 drugs. It can also submit a patient’s expression profile to predict therapeutic drugs conveniently. In summary, our research may promote the study of lncRNAs in the drug resistance mechanism and improve the effectiveness of treatment.

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Drug Response Associated With and Prognostic lncRNAs Mediated by DNA Methylation and Transcription Factors in Colon Cancer

Cited by 3 publications

References 65 publications

Oncogenic roles of the lncRNA LINC00460 in human cancers

Oncogenic roles of the lncRNA LINC00460 in human cancers

Methylation of CpG Sites as Biomarkers Predictive of Drug-Specific Patient Survival in Cancer

Identifying and characterizing drug sensitivity-related lncRNA-TF-gene regulatory triplets

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