AL360181.1 促进结肠癌的增殖和侵袭，是预测总生存期的十个 m6A 相关 lncRNA 之一。

AL360181.1 promotes proliferation and invasion in colon cancer and is one of ten m6A-related lncRNAs that predict overall survival.

机构信息

Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.

出版信息

PeerJ. 2023 Nov 8;11:e16123. doi: 10.7717/peerj.16123. eCollection 2023.

DOI:10.7717/peerj.16123

PMID:37953780

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10638913/

Abstract

BACKGROUND

N6-methyladenosine (m6A) exerted a pivotal role in colon cancer. Nevertheless, the long non-coding RNAs (lncRNAs) associated with this process have yet to be elucidated.

METHODS

The open-access data used for analysis was downloaded from The Cancer Genome Atlas (TCGA) database for analysis, employing the R software for computational evaluations. The RNA level of specific molecules was assessed using the quantitative real-time PCR. CCK8, colony formation and transwell assay were used to evaluate the proliferation, invasion and migration ability of colon cancer cells.

RESULTS

Here, we identified the m6A regulators from TCGA data and subsequently pinpointed lncRNAs with a -Cor- > 0.3 and < 0.05, categorizing them as m6A-associated lncRNAs. Moreover, we formulated a prognosis signature rooted in ten m6A-related lncRNAs, consisting of AL360181.1, PCAT6, SNHG26, AC016876.1, AC104667.2, AL114730.3, LINC02257, AC147067.1, AP006621.3 and AC009237.14. This signature exhibited notable predictive accuracy in gauging patient survival. Immune-related evaluations revealed varied immune cell infiltration patterns across different risk groups, with our findings suggesting superior immunotherapy response in low-risk patients. Biological enrichment analysis indicated that the high-risk patients had a higher activity of multiple carcinogenic pathways, including glycolysis. The previously unreported lncRNA, AL360181.1, displayed a connection to glycolytic activity and diminished survival rates, warranting further investigation. The result indicated that AL360181.1 was correlated with more aggressive clinical characteristics. Immune infiltration assessments found AL360181.1 to have a positive correlation with Tcm infiltration, but an inverse relationship with entities like Th2 cells, T cells, neutrophils and macrophages. Biological enrichment analysis indicated that the pathways of WNT/β-catenin, pancreas beta cells, hedgehog signaling and some metabolism pathways were upregulated in high AL360181.1 patients. experiments showed that AL360181.1 was upregulated in the colon cancer cells. Moreover, AL360181.1 significantly promotes the proliferation, invasion and migration of colon cancer cells.

CONCLUSIONS

Our results can provide direction for future studies on m6A-related lncRNA in colon cancer.

摘要

背景

N6-甲基腺苷（m6A）在结肠癌中发挥着关键作用。然而，与该过程相关的长非编码 RNA（lncRNA）尚未阐明。

方法

使用 R 软件进行计算评估，从癌症基因组图谱（TCGA）数据库下载用于分析的公开数据。使用定量实时 PCR 评估特定分子的 RNA 水平。CCK8、集落形成和 Transwell 测定用于评估结肠癌细胞的增殖、侵袭和迁移能力。

结果

在这里，我们从 TCGA 数据中鉴定了 m6A 调节剂，随后确定了 -Cor- > 0.3 和 < 0.05 的与 m6A 相关的 lncRNA，将其归类为 m6A 相关 lncRNA。此外，我们基于 10 个 m6A 相关 lncRNA 构建了一个预后特征，其中包括 AL360181.1、PCAT6、SNHG26、AC016876.1、AC104667.2、AL114730.3、LINC02257、AC147067.1、AP006621.3 和 AC009237.14。该特征在评估患者生存方面表现出显著的预测准确性。免疫相关评估显示不同风险组之间存在不同的免疫细胞浸润模式，我们的研究结果表明低危患者对免疫治疗的反应更好。生物富集分析表明，高危患者具有更高的多种致癌途径活性，包括糖酵解。以前未报道的 lncRNA AL360181.1 与糖酵解活性和生存率降低有关，值得进一步研究。结果表明，AL360181.1 与更具侵袭性的临床特征相关。免疫浸润评估发现 AL360181.1 与 Tcm 浸润呈正相关，但与 Th2 细胞、T 细胞、中性粒细胞和巨噬细胞呈负相关。生物富集分析表明，高 AL360181.1 患者的 WNT/β-catenin、胰腺β细胞、Hedgehog 信号通路和一些代谢途径上调。实验表明，AL360181.1 在结肠癌细胞中上调。此外，AL360181.1 显著促进结肠癌细胞的增殖、侵袭和迁移。