Dataset Information

Comprehensive analysis of lncRNAs N⁶-methyladenosine modification in colorectal cancer.

ABSTRACT:

Background

Long non-coding RNAs (lncRNAs) and their N6-methyladenosine (M6A) modifications are involved in cancer occurrence and development.

Methods

lncRNA M6A modification in colorectal cancer (CRC) was comprehensively analyzed for the first time.

Results

M6A levels of lnRNAs in CRC tissues were higher than those in tumor-adjacent normal tissues. A total of 8,332 M6A peaks were detected in 6,690 lncRNAs in CRC tissues. Approximately 91% of the modified lncRNAs had unique M6A modification peaks. A total of 383 lncRNAs were differentially methylated in CRC, of which 48.24% had a length of 1-1,000 bp. Most of these were located on chromosomes 1, 2, 7, 11, 16 and 19; 42.3% were within a sense-overlapping exon. RNA sequencing identified 163 differentially expressed lncRNAs in CRC. GO and KEGG analyses revealed that genes near differentially-methylated or -expressed lncRNAs were associated with CRC occurrence and development. Methylation was positively correlated with lncRNA expression levels in CRC and tumor-adjacent normal tissues. More unmethylated than M6A methylated lncRNA molecules were detected. A competing endogenous RNA (ceRNA) and lncRNA-mRNA expression-regulation network revealed a regulatory relationship between lncRNAs, microRNAs (miRNAs), and mRNAs.

Conclusions

The findings may help improve our understanding of lncRNA function in colorectal cancer.

SUBMITTER: Zuo L

PROVIDER: S-EPMC7906145 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Comprehensive analysis of lncRNAs N<sup>6</sup>-methyladenosine modification in colorectal cancer.

Zuo Luo L Su Hui H Zhang Qiao Q Wu Wei-Yu WY Zeng Yan Y Li Xue-Mei XM Xiong Jing J Chen Lan-Fang LF Zhou Yan Y

Aging 20210120 3

<h4>Background</h4>Long non-coding RNAs (lncRNAs) and their N6-methyladenosine (M6A) modifications are involved in cancer occurrence and development.<h4>Methods</h4>lncRNA M6A modification in colorectal cancer (CRC) was comprehensively analyzed for the first time.<h4>Results</h4>M6A levels of lnRNAs in CRC tissues were higher than those in tumor-adjacent normal tissues. A total of 8,332 M6A peaks were detected in 6,690 lncRNAs in CRC tissues. Approximately 91% of the modified lncRNAs had unique ...[more]

PMID: 33493136

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Project description:Purpose: To comprehensively analyze N6-methyladenosine modification patterns in bladder tumors and to further systematically explore the inherent relationships between these modification patterns and multiomic tumor characteristics. Materials and Methods: A total of 901 bladder tumor samples, including 405 samples from TCGA database, 188 samples from GSE13507 and 308 samples from GSE32894, were included in this systematic analysis. The N6-methyladenosine modification patterns were identified utilizing unsupervised clustering analysis. To quantify N6-methyladenosine modification patterns, the m6Ascore of individual sample was developed using principal component analysis algorithms. Relationships among immune infiltration, tumor mutation burden, various clinical characteristics, molecular subtypes, and the m6Ascore were systematically analyzed. The guiding value of m6Ascore in immunotherapy was further validated in an external trial cohort. Genomics of Drug Sensitivity in Cancer expression references were also utilized to perform drug sensitivity analysis for patients with distinct m6A modification patterns. Results: We determined three different N6-methyladenosine modification patterns for 901 bladder tumors. The quantitative m6Ascore of individual sample derived from N6-methyladenosine modification patterns could play a significant role in predicting overall survival, immune cell infiltration, and classic oncogene mutations. A low m6Ascore combined with high tumor mutation burden indicated better survival outcomes (p < 0.001). A higher m6Ascore also indicated a higher grade, higher T and N stage, elder ages, higher death rate, and higher PD1/PDL1/CTLA4 expressions (p < 0.01). The Basal type tended to exhibit significantly higher m6Ascores than the Luminal and Neuronal subtypes. External immunotherapy cohorts demonstrated that no difference in therapeutic effects was noted between the high and low m6Ascore groups when anti-PD1 immunotherapy was exclusively administered. When anti-PD1 and anti-CTLA4 immunotherapy were simultaneously administered, the high m6Ascore group had a significantly better prognosis than the low m6Ascore group (p < 0.001). High m6A groups were potentially sensitive to various medical treatments including Bleomycin, Bortezomib, Cisplatin, Cyclopamine, Dasatinib, Docetaxe, Rapamycin, and Vinblastine in this study. Conclusions: This study systematically revealed the important roles of m6A methylation modification patterns in bladder tumors. Detailed quantification of m6A modification patterns could improve our understanding of the bladder tumor microenvironments and could provide guidance for future immunotherapy strategies.

Dataset Information

Comprehensive analysis of lncRNAs N⁶-methyladenosine modification in colorectal cancer.

Background

Methods

Results

Conclusions

Publications

Comprehensive analysis of lncRNAs N<sup>6</sup>-methyladenosine modification in colorectal cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Comprehensive analysis of lncRNAs N6-methyladenosine modification in colorectal cancer.

Background

Methods

Results

Conclusions

Publications

Comprehensive analysis of lncRNAs N<sup>6</sup>-methyladenosine modification in colorectal cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Comprehensive analysis of lncRNAs N⁶-methyladenosine modification in colorectal cancer.