Dysregulation of miR-204-5p/APLN axis affects malignant progression and cell stemness of esophageal cancer

IF 1.5 4区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2022-07-01 DOI:10.1016/j.mrfmmm.2022.111791

Yifan Zhou, Ruihong Xu, Jinlong Luo, Xiangwei Li, Yonglong Zhong, Zhendong Sun

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引用次数: 1

Abstract

Objective

This study attempted to investigate the mechanism of miR-204-5p and its downstream gene in regulating bio-functions of esophageal cancer (EC).

Methods

Bioinformatics analysis was performed to select the mature miRNAs, mRNAs, and clinical data of EC. The miRNA-mRNA regulatory axis was predicted through bioinformatics and used Dual-luciferase analysis to verify the interaction between miR-204-5p and APLN. qRT-PCR was applied to analyze expression of miR-204-5p and APLN mRNA. Western blot was utilized to detect APLN protein expression. Functional assays like CCK-8, wound healing, Transwell, and stem cell sphere formation assays were launched to confirm proliferative, migratory, invasive and stemness of cells in different treatment groups.

Results

MiR-204-5p was lowly expressed while its target gene APLN was highly expressed in tumor tissues. Besides, miR-204-5p overexpression hindered proliferation, invasion, migration, and stemness of EC cells. Additionally, dual-luciferase assay verified the interaction of miR-204-5p and APLN. MiR-204-5p could downregulate APLN level and its overexpression reduced the effect of APLN on EC cell functions.

Conclusion

Dysregulation of miR-204-5p/APLN axis was linked with malignant progression of EC. MiR-204-5p/APLN may be an underlying candidate for the design of anticarcinogens.

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miR-204-5p/APLN轴异常影响食管癌的恶性进展和细胞干性

目的探讨miR-204-5p及其下游基因调控食管癌(EC)生物功能的机制。方法采用生物信息学方法筛选EC成熟mirna、mrna及临床资料。通过生物信息学预测miRNA-mRNA调控轴，并使用双荧光素酶分析验证miR-204-5p与APLN之间的相互作用。采用qRT-PCR分析miR-204-5p和APLN mRNA的表达。Western blot检测APLN蛋白表达。开展CCK-8、创面愈合、Transwell、干细胞球形成等功能测定，确认不同处理组细胞的增殖、迁移、侵袭性和干性。结果smir -204-5p在肿瘤组织中低表达，其靶基因APLN在肿瘤组织中高表达。此外，miR-204-5p过表达抑制了EC细胞的增殖、侵袭、迁移和干性。此外，双荧光素酶测定证实了miR-204-5p与APLN的相互作用。MiR-204-5p可下调APLN水平，其过表达可降低APLN对EC细胞功能的影响。结论miR-204-5p/APLN轴表达异常与EC恶性进展有关。MiR-204-5p/APLN可能是设计抗癌药物的潜在候选者。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis 生物-毒理学

CiteScore

4.90

自引率

0.00%

发文量

审稿时长

51 days

期刊介绍： Mutation Research (MR) provides a platform for publishing all aspects of DNA mutations and epimutations, from basic evolutionary aspects to translational applications in genetic and epigenetic diagnostics and therapy. Mutations are defined as all possible alterations in DNA sequence and sequence organization, from point mutations to genome structural variation, chromosomal aberrations and aneuploidy. Epimutations are defined as alterations in the epigenome, i.e., changes in DNA methylation, histone modification and small regulatory RNAs. MR publishes articles in the following areas: Of special interest are basic mechanisms through which DNA damage and mutations impact development and differentiation, stem cell biology and cell fate in general, including various forms of cell death and cellular senescence. The study of genome instability in human molecular epidemiology and in relation to complex phenotypes, such as human disease, is considered a growing area of importance. Mechanisms of (epi)mutation induction, for example, during DNA repair, replication or recombination; novel methods of (epi)mutation detection, with a focus on ultra-high-throughput sequencing. Landscape of somatic mutations and epimutations in cancer and aging. Role of de novo mutations in human disease and aging; mutations in population genomics. Interactions between mutations and epimutations. The role of epimutations in chromatin structure and function. Mitochondrial DNA mutations and their consequences in terms of human disease and aging. Novel ways to generate mutations and epimutations in cell lines and animal models.