LncRNA PTPRG-AS1 Promotes Breast Cancer Progression by Modulating the miR-4659a-3p/QPCT Axis.

IF 2.7 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY OncoTargets and therapy Pub Date : 2024-10-04 eCollection Date: 2024-01-01 DOI:10.2147/OTT.S474898

Mengsi Zhou, Yanting Li, Liu Yang, Shuo Liu, Lixian Yang, Bin Xu, Xiaolong Li, Quanle Wang, Haijun Zhao, Zhenchuan Song

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Abstract

Background: Overwhelming evidence has suggested that dysregulated long noncoding RNAs (lncRNAs) play a critical modulating effect in the evolution of breast cancer (BRCA). Nevertheless, the roles of lncRNA PTPRG antisense RNA 1 (PTPRG-AS1) in BRCA and the underlying mechanisms have not been experimentally validated and functionally annotated.

Methods: The expression of lncRNA PTPRG-AS1 in BRCA tissues and cell lines was evaluated by reverse transcription-quantitative PCR (RT-qPCR), and by using public databases. The proliferation of BRCA cells was detected using Cell Counting Kit-8 and colony formation assays. Wound healing assay, and Transwell migration and invasion assays were carried out to explore the migratory and invasive abilities of BRCA cells. The interaction between lncRNA PTPRG-AS1, microRNA (miR)-4659a-3p and glutaminyl-peptide cyclotransferase (QPCT) was verified using RT-qPCR, dual-luciferase reporter assay and Western blotting.

Results: The results showed that LncRNA PTPRG-AS1 was markedly upregulated in BRCA tissues and cell lines. Knocking down lncRNA PTPRG-AS1 significantly inhibited the proliferation, migration and invasion of BRCA cells, while overexpression of lncRNA PTPRG-AS1 enhanced the aforementioned properties of BRCA cells. Further analyses revealed that PTPRG-AS1 may act as a molecular sponge for miR-4659a-3p, thus regulating QPCT expression, therefore, acting as an oncogene in BRCA.

Conclusion: Collectively, the study demonstrates that lncRNA PTPRG-AS1 may act as a competing endogenous RNA by regulating the miR-4659a-3p/QPCT axis in BRCA progression. This lncRNA could potentially be a biomarker and therapeutic target for BRCA.

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LncRNA PTPRG-AS1 通过调节 miR-4659a-3p/QPCT 轴促进乳腺癌进展

背景：大量证据表明，失调的长非编码RNA（lncRNA）在乳腺癌（BRCA）的进化过程中起着关键的调节作用。然而，lncRNA PTPRG反义RNA 1（PTPRG-AS1）在BRCA中的作用及其内在机制尚未得到实验验证和功能注释：方法：通过反转录-定量 PCR（RT-qPCR）和使用公共数据库评估了 lncRNA PTPRG-AS1 在 BRCA 组织和细胞系中的表达。使用细胞计数试剂盒-8 和集落形成试验检测 BRCA 细胞的增殖情况。伤口愈合试验、Transwell 迁移和侵袭试验用于探究 BRCA 细胞的迁移和侵袭能力。利用 RT-qPCR、双荧光素酶报告实验和 Western 印迹法验证了 lncRNA PTPRG-AS1、microRNA (miR)-4659a-3p 和谷氨酰肽环转酶（QPCT）之间的相互作用：结果表明，LncRNA PTPRG-AS1在BRCA组织和细胞系中明显上调。敲除lncRNA PTPRG-AS1可显著抑制BRCA细胞的增殖、迁移和侵袭，而过表达lncRNA PTPRG-AS1可增强BRCA细胞的上述特性。进一步的分析表明，PTPRG-AS1可能是miR-4659a-3p的分子海绵，从而调节QPCT的表达，因此在BRCA中起着癌基因的作用：总之，该研究表明，lncRNA PTPRG-AS1 可通过调节 miR-4659a-3p/QPCT 轴，在 BRCA 进展过程中充当竞争性内源性 RNA。这种 lncRNA 有可能成为 BRCA 的生物标志物和治疗靶点。

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

OncoTargets and therapy BIOTECHNOLOGY & APPLIED MICROBIOLOGY-ONCOLOGY

CiteScore

9.70

自引率

0.00%

发文量

221

审稿时长

1 months

期刊介绍： OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer. The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype. Specific topics covered by the journal include: -Novel therapeutic targets and innovative agents -Novel therapeutic regimens for improved benefit and/or decreased side effects -Early stage clinical trials Further considerations when submitting to OncoTargets and Therapy: -Studies containing in vivo animal model data will be considered favorably. -Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines. -Biomarker association studies will be considered only when validated by comprehensive in vitro data and analysis of human tissue samples. -Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Single nucleotide polymorphism (SNP) studies will not be considered.