Zhou Mengsi, Li Yanting, Yang Liu, Liu Shuo, Yang Lixian, Xu Bin, Li Xiaolong, Wang Quanle, Zhao Haijun, Song Zhenchuan
Department of Breast and Thyroid Surgery, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People's Republic of China.
Department of Breast Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050035, People's Republic of China.
Onco Targets Ther. 2024 Oct 4;17:805-819. doi: 10.2147/OTT.S474898. eCollection 2024.
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.
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.
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.
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.
大量证据表明,长链非编码RNA(lncRNA)失调在乳腺癌(BRCA)的进展中起关键调节作用。然而,lncRNA PTPRG反义RNA 1(PTPRG-AS1)在BRCA中的作用及其潜在机制尚未得到实验验证和功能注释。
通过逆转录定量PCR(RT-qPCR)并利用公共数据库评估BRCA组织和细胞系中lncRNA PTPRG-AS1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。进行伤口愈合试验、Transwell迁移和侵袭试验以探究BRCA细胞的迁移和侵袭能力。使用RT-qPCR、双荧光素酶报告基因试验和蛋白质免疫印迹法验证lncRNA PTPRG-AS1、微小RNA(miR)-4659a-3p和谷氨酰胺肽环转移酶(QPCT)之间的相互作用。
结果显示,lncRNA PTPRG-AS1在BRCA组织和细胞系中显著上调。敲低lncRNA PTPRG-AS1可显著抑制BRCA细胞的增殖、迁移和侵袭,而lncRNA PTPRG-AS1的过表达增强了BRCA细胞的上述特性。进一步分析表明,PTPRG-AS1可能作为miR-4659a-3p的分子海绵,从而调节QPCT的表达,因此,在BRCA中作为癌基因发挥作用。
总体而言,该研究表明lncRNA PTPRG-AS1可能通过在BRCA进展中调节miR-4659a-3p/QPCT轴而作为竞争性内源RNA发挥作用。这种lncRNA可能是BRCA的潜在生物标志物和治疗靶点。