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miR-21 在肺癌中作用的可能分子机制

Possible Molecular Mechanisms for the Roles of MicroRNA-21 Played in Lung Cancer.

机构信息

Department of Orthopedics, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Technol Cancer Res Treat. 2019 Jan 1;18:1533033819875130. doi: 10.1177/1533033819875130.

DOI:10.1177/1533033819875130
PMID:31506038
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6740056/
Abstract

BACKGROUND

We aimed to find the possible molecular mechanisms for the roles of microRNA-21 underlying lung cancer development.

METHODS

MicroRNA-21-5p inhibitor was transfected into A549 cells. Total RNA was isolated from 10 samples, including 3 in control group (A549 cells), 3 in negative control group (A549 cells transferred with microRNA-21 negative control), and 4 in SH group (A549 cells transferred with microRNA-21 inhibitor), followed by RNA sequencing. Then, differentially expressed genes were screened for negative control group versus control group, SH group versus control group, and SH group versus negative control group. Functional enrichment analyses, protein-protein interaction network, and modules analyses were conducted. Target genes of hsa-miR-21-5p and transcription factors were predicted, followed by the regulatory network construction.

RESULTS

Minichromosome maintenance 10 replication initiation factor and cell division cycle associated 8 were important nodes in protein-protein interaction network with higher degrees. Cell division cycle associated 8 was enriched in cell division biological process. Furthermore, maintenance 10 replication initiation factor and cell division cycle associated 8 were significantly enriched in cluster 1 and micro-RNA-transcription factor-target genes regulating network. In addition, transcription factor Dp family member 3 (transcription factor of maintenance 10 replication initiation factor and cell division cycle associated 8) and RAD21 cohesin complex component (transcription factor of maintenance 10 replication initiation factor) were target genes of hsa-miR-21-5p.

CONCLUSIONS

Micro-RNA-21 may play a key role in lung cancer partly via maintenance 10 replication initiation factor and cell division cycle associated 8. Furthermore, microRNA-21 targeted cell division cycle associated 8 and then played roles in lung cancer via the process of cell division. Transcription factor Dp family member 3 and RAD21 cohesin complex component are important transcription factors in microRNA-21-interfered lung cancer.

摘要

背景

我们旨在寻找 microRNA-21 在肺癌发展中作用的可能分子机制。

方法

将 microRNA-21-5p 抑制剂转染至 A549 细胞。从 10 个样本中分离总 RNA,包括对照组(A549 细胞)中的 3 个样本、阴性对照组(转染 microRNA-21 阴性对照的 A549 细胞)中的 3 个样本和 SH 组(转染 microRNA-21 抑制剂的 A549 细胞)中的 4 个样本,随后进行 RNA 测序。然后,筛选阴性对照组与对照组、SH 组与对照组、SH 组与阴性对照组之间差异表达的基因。进行功能富集分析、蛋白质-蛋白质相互作用网络和模块分析。预测 hsa-miR-21-5p 的靶基因和转录因子,然后构建调控网络。

结果

微染色体维持蛋白 10 复制起始因子和细胞分裂周期相关蛋白 8 是蛋白质-蛋白质相互作用网络中具有较高度数的重要节点。细胞分裂周期相关蛋白 8 在细胞分裂的生物学过程中富集。此外,维持蛋白 10 复制起始因子和细胞分裂周期相关蛋白 8 在簇 1 和微 RNA-转录因子-靶基因调控网络中显著富集。另外,DP 家族成员 3(维持蛋白 10 复制起始因子和细胞分裂周期相关蛋白 8 的转录因子)和 RAD21 黏合复合物成分(维持蛋白 10 复制起始因子的转录因子)是 hsa-miR-21-5p 的靶基因。

结论

miRNA-21 可能通过维持蛋白 10 复制起始因子和细胞分裂周期相关蛋白 8 在肺癌中发挥关键作用。此外,miRNA-21 靶向细胞分裂周期相关蛋白 8,然后通过细胞分裂过程在肺癌中发挥作用。DP 家族成员 3 和 RAD21 黏合复合物成分是 miRNA-21 干扰肺癌中的重要转录因子。

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