乳腺癌是女性最常见的恶性肿瘤之一，并造成大量癌症相关死亡。乳腺癌患者死亡的主要原因是肿瘤复发和转移。最近的研究表明长链非编码RNA（lncRNA）在乳腺癌中起着重要作用。然而，lncRNA MIR17HG在乳腺癌中的整体生物活性和临床后果仍不清楚。因此，我们研究了MIR17HG/miR-454-3p网络如何影响乳腺癌细胞的增殖和迁移。在TCGA和Oncomine数据库的基础上，研究人员评估了MIR17HG表达变异对乳腺癌患者生存率的影响。确定了MIR17HG对细胞增殖、迁移、细胞周期和miR-454-3p和FAM135A（序列相似性家族135成员A）mRNA表达水平的影响。使用荧光素酶分析检测miR-454-3p对FAM135A 3'UTR区域的调控效应，恢复实验证明MIR17HG通过与miR-454-3p竞争性结合来上调FAM135A表达。检测了FAM135A对MCF-7细胞克隆和侵袭的影响。乳腺癌组织中MIR17HG的表达降低，表达水平较高的患者预后较好。根据流式细胞术分析，MIR17HG过表达可导致乳腺癌细胞处于G2/M期阻滞状态。FAM135A敲低增强了乳腺癌细胞增殖和克隆创建能力，以及二维和三维迁移能力。乳腺癌中FAM135A表达高的患者预后较好。这些新发现表明MIR17HG可能是乳腺癌的一个潜在靶点。我们的发现表明MIR17HG可能通过ceRNA（竞争性内源性RNA）机制，通过海绵miR-454-3p抑制乳腺癌细胞的增殖和迁移，进而成为乳腺癌治疗的可行候选药物。©2023. 作者

Breast cancer is one of the most common malignant tumors in women, and causes a large number of cancer-related deaths. The main cause of death of breast cancer patients is tumor recurrence and metastasis. Recent studies show that lncRNA (Long non-coding RNA) plays an important role in breast cancer. However, the overall biological activity and clinical consequences of the lncRNA MIR17HG in breast cancer remain unclear. Thus, we investigate how the MIR17HG/miR-454-3p network impacts breast cancer cell proliferation and migration. Given the TCGA and Oncomine databases, the researchers evaluated variations in MIR17HG expression for the survival rates of breast cancer patients. The influence of MIR17HG on cell proliferation, migration, cell cycle, and the mRNA expression level of miR-454-3p and FAM135A (family with sequence similarity 135 member A) is identified. Luciferase assay was used to detect the regulatory effect of miR-454-3p on the 3'UTR region of FAM135A, and rescue experiments demonstrated that MIR17HG can up-regulate FAM135A expression by competitively binding miR-454-3p. The effect of FAM135A on the cloning and invasion of MCF-7 cells was detected. MIR17HG expression is reduced in breast cancer tissues, and patients with greater levels of MIR17HG expression have a better prognosis. MIR17HG overexpression caused G2/M arrest in breast cancer cells according to a flow cytometry assay. FAM135A knockdown enhances breast cancer cell proliferation and clone creation, as well as two-dimensional and three-dimensional migratory capacities. Patients with high FAM135A expression in their breast cancer had a better prognosis. These novel findings indicate that MIR17HG may be a potential target for breast cancer. Our findings demonstrated that MIR17HG might suppress breast cancer cell proliferation and migration by sponge miR-454-3p through ceRNA(competing endogenous RNAs) mechanism, indicating that targeting MIR17HG may be a feasible therapeutic candidate for breast cancer.© 2023. The Author(s).