miR-4469作为一种调节结直肠癌炎症细胞浸润的肿瘤抑制因子的作用。

The role of miR-4469 as a tumor suppressor regulating inflammatory cell infiltration in colorectal cancer.

作者信息

Qi Lu, Wang Lu, Song Fuyao, Ding Zhenhua, Zhang Ying

机构信息

Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.

出版信息

Comput Struct Biotechnol J. 2022 Jul 14;20:3755-3763. doi: 10.1016/j.csbj.2022.07.021. eCollection 2022.

DOI:10.1016/j.csbj.2022.07.021

PMID:35891783

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9304430/

Abstract

BACKGROUND

MicroRNA (miRNA) regulates gene expression posttranscriptionally, and some of them function in tumor suppression and can be used in drug development. As a result, identifying and screening miRNAs that suppress tumors would be a significant addition to tumor treatment.

METHODS

In this study, we analyzed the miRNA expression profile of colorectal cancer (CRC), constructed a negative regulatory network of the miRNA-target genes, and identified miR-4469 as one of the key tumor suppressors miRNAs. We analyzed the expression and survival of miR-4469 in pan-cancer, experimentally verified the expression level of miR-4469 in CRC cells and the effect on CRC cell proliferation and migration. We screened miR-4469 target genes for enrichment analysis and immune cell infiltration analysis and validated target gene expression to clarify the regulatory mechanisms involved in miR-4469.

RESULTS

miR-4469 was more highly expressed in normal colorectum tissues compared to CRC tissues and correlated with survival time in patients with multiple cancers. It was shown that miR-4469 was highly expressed in normal colon cells and miR-4469 expression could inhibit the proliferation and migration of CRC cells. In addition, studies on the mechanism showed that miR-4469 function is mainly related to the regulation of inflammatory cell infiltration, and the key target genes of miR-4469 in this process are SLC2A3, FGR, PLEKHO2, and MYO1F.

CONCLUSION

miR-4469 is a tumor suppressor in CRC, and its regulatory mechanism mainly affects the infiltration of inflammatory cells in the cancer tissue.

摘要

背景

微小RNA（miRNA）在转录后调节基因表达，其中一些具有肿瘤抑制功能，可用于药物开发。因此，鉴定和筛选抑制肿瘤的miRNA将为肿瘤治疗增添重要内容。

方法

在本研究中，我们分析了结直肠癌（CRC）的miRNA表达谱，构建了miRNA-靶基因的负调控网络，并确定miR-4469是关键的肿瘤抑制miRNA之一。我们分析了miR-4469在泛癌中的表达和生存情况，通过实验验证了miR-4469在CRC细胞中的表达水平及其对CRC细胞增殖和迁移的影响。我们筛选了miR-4469靶基因进行富集分析和免疫细胞浸润分析，并验证了靶基因表达以阐明miR-4469涉及的调控机制。

结果

与CRC组织相比，miR-4469在正常结直肠组织中表达更高，且与多种癌症患者的生存时间相关。结果表明，miR-4469在正常结肠细胞中高表达，miR-4469的表达可抑制CRC细胞的增殖和迁移。此外，机制研究表明，miR-4469的功能主要与炎症细胞浸润的调节有关，在此过程中miR-4469的关键靶基因是SLC2A3、FGR、PLEKHO2和MYO1F。