Comprehensive analysis of lncRNAs N6-methyladenosine modification in colorectal cancer

Zuo, Luo; Su, Hui; Zhang, Qiao; Wu, Weiyu; Zeng, Yan; Li, Xuemei; Xiong, Jing; Lan-fang, Chen; Zhou, Yan

doi:10.18632/aging.202383

Cited by 19 publications

(17 citation statements)

References 54 publications

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“…Similarly, Yuan et al constructed a lncRNAs prognostic model in liver cancer, and twenty-seven immune-related lncRNAs were screened by univariate Cox regression, the results show that AL049840.4 has prognostic value in liver cancer [35]. In addition, Zuo et al found that the m6A level of lncRNAs in CRC tissue was significantly higher than that in NATs and the GO and KEGG results showed that the lncRNAs modified by m6A can affect the occurrence and development of CRC by biological processes, cell composition, and molecular function [36]. These results suggest that lncRNA plays a vital role in predicting tumor prognosis and clarifies the relationship between lncRNA and m6A, which is beneficial to discovering new targets and treating tumors.…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of a Novel 2-LncRNAs Signature Associated with m6A Regulation in Colorectal Cancer

Wang¹,

Zhao²,

Ma³

2022

J. Cancer

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Colorectal cancer (CRC) is one of the most common tumors in the digestive system, and it is urgent to identify a new biomarker for the diagnosis and treatment of CRC. N6-methyladenosine (m6A) is an abundant mRNA modification and is almost involved in every aspect of physiological processes. In this study, we constructed a novel m6A-related 2-lncRNAs signature that can predict the prognosis of CRC. We obtained m6A-related lncRNAs and identified prognostic lncRNAs through univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis, then constructed a prognostic model based on the risk score, and we also verified the stability of the model. In addition, differential expression analysis between the high-and low-risk subgroups was performed. A total of 1,894 m6A-related lncRNAs were screened from various sources. Using univariate Cox regression analysis and survival analysis, two lncRNAs (AL135999.1 and AL049840.4) were identified (P < 0.05), and the coefficients of lncRNAs were calculated by LASSO. The high-risk group had worse clinical outcomes and overall survival (OS) than the low-risk group, and the risk score can serve as an independent prognostic factor in CRC. In addition, different stages of CRC also showed a different level of risk score. Finally, we found that two lncRNAs were differentially expressed (P < 0.01) in CRC patients, and AL135999.1 may be relevant to m6A modification mediated by methyltransferase-like 3 (METTL3) in CRC. In summary, we constructed a reliable 2-lncRNAs signature based on the risk score, and we identified two m6A-related prognostic lncRNAs, AL135999.1 and AL049840.4. The novel 2-lncRNAs signature plays an essential role in predicting the prognosis of CRC.

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Section: Discussionmentioning

confidence: 99%

Identification and Validation of a Novel 2-LncRNAs Signature Associated with m6A Regulation in Colorectal Cancer

Wang¹,

Zhao²,

Ma³

2022

J. Cancer

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“…Methylation was positively correlated with lncRNA expression levels in CRC and normal tissues adjacent to tumors. 45 …”

Section: M6a Rna Modificationmentioning

confidence: 99%

“…About 91% of the modified lncRNAs had a unique m6A modification peak, and a total of 383 lncRNAs were differentially methylated in CRC. 101 Ni et al found that lncRNA GAS5 expression negatively correlates with YAP and YTHDF3 protein levels in tumors from patients with CRC, and YAP activation is an important participant in a variety of cancers including CRC. The researchers found that the lncRNA GAS5 modified by m6A is negatively regulated by m6A “readers” YTHDF3, and further inhibits the progress of CRC by interacting with YAP to trigger its phosphorylation and degradation process.…”

Section: M6a Rna Methylation Modification and Colorectal Cancermentioning

confidence: 99%

“…Methylation was positively correlated with lncRNA expression levels in CRC and normal tissues adjacent to tumors. 45 Similarly, Liu et al showed that the internal m6A modification of lncRNA Thor modulates cancer cell proliferation in an m6A reader-dependent manner. Specific m6A readers YTHDF1 and YTHDF2 can read the highly enriched m6A motif on lncRNA Thor transcripts, regulate its stability, and thus maintain the carcinogenic effect.…”

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confidence: 96%

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The Emerging Clinical Application of m6A RNA Modification in Inflammatory Bowel Disease and Its Associated Colorectal Cancer

Xu¹,

Huang²,

Ocansey³

et al. 2021

JIR

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Methylation, first proposed in DNAs, but later found in RNAs, serves as one of the most widespread epigenetic modifications in eukaryotes, where N6-methyladenosine (m6A) modification has been found to play an important role in a variety of cancers including colorectal cancer (CRC). Under the action of various enzymes and proteins, the regulatory role of m6A in RNAs and immune cells has also been gradually realized. This paper reviews the general biogenesis and effects of m6A, and its emerging crucial role in intestinal mucosal immunity via the regulation of RNAs and immune cells, and thus closely related to the occurrence and development of inflammatory bowel disease (IBD) and CRC. m6A-related genes and regulatory factors are expected to be potential predictive markers and therapeutic targets.

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“…Recent studies have demonstrated that m6A-related lncRNAs can reliably predict the prognosis of low-grade glioma, lung adenocarcinoma, and gastric cancer ( Tu et al, 2020 ; Wang et al, 2021a ; Wang et al, 2021b ). Luo et al( Zuo et al, 2021 ) further observed that m6A-related lncRNAs were associated with the occurrence and development of CRC, indicating that they may be an accurate prognostic factor for early-stage CRC.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of N6-Methyladenosine-Related lncRNAs in Early-Stage Colorectal Cancer: Association With Immune Cell Infiltration and Chemotherapeutic Drug Sensitivity

Xiong

Yin

et al. 2021

Front. Mol. Biosci.

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Purpose: Accumulating evidence indicates that N6-methyladenosine-related long non-coding RNAs (m6A-related lncRNAs) play a crucial role in the occurrence and development of several cancers. We aimed to explore the potential role of m6A-related lncRNA signatures in predicting prognosis for early-stage (stages I and II) colorectal cancer (CRC).Methods: m6A-related lncRNA data were obtained from The Cancer Genome Atlas. Univariate Cox regression analysis was used to screen for prognostic m6A-related lncRNAs. Immune characteristics were analyzed in different subgroups created via unsupervised clustering analysis. Next, patients were randomly divided into training and test cohorts. In the training cohort, least absolute shrinkage and selection operator (LASSO) regression was performed to establish a prognostic model. The predictive value of the signature was evaluated in the training and test cohorts. Drug sensitivity was also examined.Results: A total of 1,478 m6A-related lncRNAs were identified. Two subgroups were created based on the expression of seven prognostic m6A-related lncRNAs. Prognosis was worse for cluster 1 than for cluster 2, and cluster 1 was characterized by increased numbers of M2 macrophages, decreased numbers of memory B cells, and higher expression of checkpoint genes when compared with cluster 2. Five m6A-related lncRNAs were selected to establish a risk prediction signature via LASSO regression. The 3 years overall survival (OS) was higher in the low-risk group than in the high-risk group. The area under the curve at 1, 2, and 3 years was 0.929, 0.954, and 0.841 in the training cohort and 0.664, 0.760, and 0.754 in the test cohort, respectively. Multivariate Cox regression analysis suggests that the risk score was an independent predictor of OS in both the training and test cohorts. A prognostic nomogram based on the five m6A-related lncRNAs and their clinical features was built and verified. The high-risk group was more sensitive to chemotherapeutic drugs (camptothecin and cisplatin) than the low-risk group.Conclusion: We identified two molecular subgroups of early-stage CRC with unique immune features based on seven prognostic m6A-related lncRNAs. Subsequent analyses demonstrated the usefulness of a five m6A-related lncRNA signature as a potential indicator of prognosis in patients with early-stage CRC.

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Comprehensive analysis of lncRNAs N6-methyladenosine modification in colorectal cancer

Cited by 19 publications

References 54 publications

Identification and Validation of a Novel 2-LncRNAs Signature Associated with m6A Regulation in Colorectal Cancer

Identification and Validation of a Novel 2-LncRNAs Signature Associated with m6A Regulation in Colorectal Cancer

The Emerging Clinical Application of m6A RNA Modification in Inflammatory Bowel Disease and Its Associated Colorectal Cancer

Prognostic Value of N6-Methyladenosine-Related lncRNAs in Early-Stage Colorectal Cancer: Association With Immune Cell Infiltration and Chemotherapeutic Drug Sensitivity

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