Department of Breast Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Mol Med Rep. 2024 Jun;29(6). doi: 10.3892/mmr.2024.13217. Epub 2024 Apr 5.
Emerging scientific evidence has suggested that the long non‑coding (lnc)RNA differentiation antagonizing non‑protein coding RNA () serves a significant role in human tumorigenesis and cancer progression; however, the precise mechanism of its function in breast cancer remains to be fully understood. Therefore, the objective of the present study was to manipulate expression in MCF7 and MDA‑MB‑231 cells using lentiviral vectors to knock down or overexpress . This manipulation, alongside the analysis of bioinformatics data, was performed to investigate the potential mechanism underlying the role of in cancer. The mRNA and/or protein expression levels of , and E2F transcription factor 1 () were assessed using reverse transcription‑quantitative PCR and western blotting, respectively. The interactions between these molecules were validated using chromatin immunoprecipitation and dual‑luciferase reporter assays. Additionally, fluorescence in situ hybridization was used to confirm the subcellular localization of . Cell proliferation, migration and invasion were determined using 5‑ethynyl‑2'‑deoxyuridine, wound healing and Transwell assays, respectively. The results of the present study demonstrated that DANCR had a regulatory role as a competing endogenous RNA and upregulated the expression of by sequestering in breast cancer cells. Furthermore, promoted transcription by binding to its promoter in breast cancer cells. Notably, the feedback loop enhanced cell proliferation, migration and invasion in breast cancer cells. Thus, these findings suggested that targeting may potentially provide a promising future therapeutic strategy for breast cancer treatment.
新兴的科学证据表明，长非编码 RNA（lncRNA）分化拮抗非蛋白编码 RNA（）在人类肿瘤发生和癌症进展中发挥重要作用；然而，其在乳腺癌中的功能的确切机制仍有待充分理解。因此，本研究的目的是使用慢病毒载体操纵 MCF7 和 MDA-MB-231 细胞中的表达，以敲低或过表达。通过分析生物信息学数据，对在癌症中发挥作用的的潜在机制进行了研究。使用逆转录定量 PCR 和 Western blot 分别评估、和 E2F 转录因子 1（）的 mRNA 和/或蛋白表达水平。使用染色质免疫沉淀和双荧光素酶报告基因测定验证这些分子之间的相互作用。此外，还使用荧光原位杂交来确认的亚细胞定位。使用 5-乙炔基-2'-脱氧尿苷测定细胞增殖，使用划痕愈合和 Transwell 测定测定细胞迁移和侵袭。本研究的结果表明，DANCR 作为竞争性内源性 RNA 具有调节作用，通过在乳腺癌细胞中隔离 sequesters 来上调的表达。此外，通过结合其启动子在乳腺癌细胞中促进转录。值得注意的是，的反馈环增强了乳腺癌细胞的增殖、迁移和侵袭。因此，这些发现表明，靶向可能为乳腺癌的治疗提供一种有前途的未来治疗策略。
