Department of Breast and Thyroid Surgery, Huaihe Hospital, Henan University, No.115, Ximen Avenue, Kaifeng, 475000, Henan Province, People's Republic of China.
Department of Obstetrics and Gynecology, Huaihe Hospital, Henan University, Kaifeng, 475000, People's Republic of China.
Clin Transl Oncol. 2023 Jul;25(7):2192-2203. doi: 10.1007/s12094-023-03102-y. Epub 2023 Mar 2.
As ceRNA network of long non-coding RNA (lncRNA)-microRNA (miR)-messenger RNAs (mRNA) can be predicted on the basis of bioinformatics tools, we are now one step closer to deeper understanding carcinogenic mechanisms. In this study, we clarified the mechanistic understanding of JHDM1D-AS1-miR-940-ARTN ceRNA network in the development of breast cancer (BC).
The lncRNA-miRNA-mRNA interaction of interest was predicted by in silico analysis and identified by conducting RNA immunoprecipitation, RNA pull-down and luciferase assays. The expression patterns of JHDM1D-AS1, miR-940 and ARTN in BC cells were altered by lentivirus infection and plasmid transfection for functional assays on the biological properties of BC cells. Finally, the tumorigenic and metastatic abilities of BC cells were assessed in vivo.
JHDM1D-AS1 was highly expressed, while miR-940 was poorly expressed in BC tissues and cells. JHDM1D-AS1 could competitively bind to miR-940, whereby promoting the malignant behaviors of BC cells. Furthermore, ARTN was identified as a target gene of miR-940. Through targeting ARTN, miR-940 exerted a tumor-suppressive role. In vivo experiments further confirmed that JHDM1D-AS1 enhanced the tumorigenesis and metastasis through up-regulation of ARTN.
Taken together, our study demonstrated the involvement of ceRNA network JHDM1D-AS1-miR-940-ARTN in the progression of BC, which highlighted promising therapeutic targets for BC treatment.
由于长链非编码 RNA（lncRNA）-微小 RNA（miR）-信使 RNA（mRNA）的 ceRNA 网络可以基于生物信息学工具进行预测，因此我们现在对致癌机制的理解又进了一步。在这项研究中，我们阐明了 JHDM1D-AS1-miR-940-ARTN ceRNA 网络在乳腺癌（BC）发展中的作用机制。
通过计算机分析预测感兴趣的 lncRNA-miRNA-mRNA 相互作用，并通过 RNA 免疫沉淀、RNA 下拉和荧光素酶测定进行鉴定。通过慢病毒感染和质粒转染改变 BC 细胞中 JHDM1D-AS1、miR-940 和 ARTN 的表达模式，进行 BC 细胞生物学特性的功能测定。最后，在体内评估 BC 细胞的致瘤和转移能力。
JHDM1D-AS1 在 BC 组织和细胞中高表达，而 miR-940 表达水平较低。JHDM1D-AS1 可以与 miR-940 竞争性结合，从而促进 BC 细胞的恶性行为。此外，ARTN 被鉴定为 miR-940 的靶基因。通过靶向 ARTN，miR-940 发挥了肿瘤抑制作用。体内实验进一步证实，JHDM1D-AS1 通过上调 ARTN 增强了肿瘤的发生和转移。
综上所述，我们的研究表明 ceRNA 网络 JHDM1D-AS1-miR-940-ARTN 参与了 BC 的进展，为 BC 的治疗提供了有希望的治疗靶点。
