Department of Breast Surgery, the First Hospital of Jilin University, Changchun, 130021, Jilin, China.
Cancer Gene Ther. 2022 Jul;29(7):951-960. doi: 10.1038/s41417-021-00388-4. Epub 2021 Oct 13.
Mounting evidence suggests that lncRNAs can exert functions in cancer progression in multiple manners. In recent years, competing endogenous RNA (ceRNA) has been widely reported in human cancers as a lncRNA-dominant molecular pathway. The current study aimed at proving the role of lncRNA downregulated RNA in cancer (DRAIC) in breast cancer (BRCA) progression. To be specific, qRT-PCR assay was conducted to measure the expression of DRAIC and other downstream target genes. It was uncovered that DRAIC was expressed at a high level in BRCA cells. Functional analyses, including CCK-8, colony formation, and EdU assays demonstrated that DRAIC depletion suppressed BRCA cell proliferation. In addition, cell apoptosis was promoted due to DRAIC knockdown. The inhibitory effect of DRAIC reduction on BRCA cell migration and invasion was proven by transwell assays. Mechanistically, DRAIC was confirmed to predominantly distribute in the cytoplasm and could interact with miR-432-5p. In addition, stem-loop binding protein (SLBP) was verified to be a downstream target of miR-432-5p and was positively regulated by DRAIC. Taken together, DRAIC sponged miR-432-5p to enhance SLBP expression, by which malignant behaviors of BRCA cells were promoted. Our findings may help to provide a promising therapeutic target for BRCA patients.
越来越多的证据表明,lncRNAs 可以通过多种方式在癌症进展中发挥作用。近年来,竞争内源性 RNA (ceRNA) 在人类癌症中作为以 lncRNA 为主的分子途径被广泛报道。本研究旨在证明下调 RNA 在癌症中的作用 (DRAIC) 在乳腺癌 (BRCA) 进展中的作用。具体来说,通过 qRT-PCR 测定来测量 DRAIC 和其他下游靶基因的表达。结果表明,DRAIC 在 BRCA 细胞中表达水平较高。功能分析,包括 CCK-8、集落形成和 EdU 测定表明,DRAIC 耗竭抑制 BRCA 细胞增殖。此外,由于 DRAIC 敲低,细胞凋亡得到促进。通过 Transwell 测定证明了 DRAIC 减少对 BRCA 细胞迁移和侵袭的抑制作用。从机制上讲,DRAIC 被证实主要分布在细胞质中,并可以与 miR-432-5p 相互作用。此外,茎环结合蛋白 (SLBP) 被验证为 miR-432-5p 的下游靶标,并被 DRAIC 正向调控。总之,DRAIC 吸附 miR-432-5p 以增强 SLBP 的表达,从而促进 BRCA 细胞的恶性行为。我们的研究结果可能有助于为 BRCA 患者提供有希望的治疗靶点。