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.

Graphical Abstract

中文翻译：

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LncRNA MIR17HG 通过海绵 miR-454-3p 作为 ceRNA 靶向 FAM135A 抑制乳腺癌增殖和迁移

乳腺癌是女性最常见的恶性肿瘤之一，导致大量癌症相关死亡。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，lncRNA（长链非编码RNA）在乳腺癌中发挥着重要作用。然而，lncRNA MIR17HG 在乳腺癌中的总体生物学活性和临床后果仍不清楚。因此，我们研究 MIR17HG/miR-454-3p 网络如何影响乳腺癌细胞增殖和迁移。根据 TCGA 和 Oncomine 数据库，研究人员评估了 MIR17HG 表达的变化对乳腺癌患者生存率的影响。确定了 MIR17HG 对细胞增殖、迁移、细胞周期以及 miR-454-3p 和 FAM135A（具有序列相似性的家族 135 成员 A）的 mRNA 表达水平的影响。采用荧光素酶实验检测miR-454-3p对FAM135A 3'UTR区的调控作用，拯救实验证明MIR17HG可以通过竞争性结合miR-454-3p上调FAM135A的表达。检测FAM135A对MCF-7细胞克隆和侵袭的影响。乳腺癌组织中MIR17HG表达减少，MIR17HG表达水平较高的患者预后较好。根据流式细胞术检测，MIR17HG 过度表达导致乳腺癌细胞 G2/M 期停滞。FAM135A 敲低可增强乳腺癌细胞增殖和克隆创建，以及二维和三维迁移能力。乳腺癌中 FAM135A 高表达的患者预后较好。这些新发现表明 MIR17HG 可能是乳腺癌的潜在靶点。我们的研究结果表明，MIR17HG 可能通过 ceRNA（竞争性内源性 RNA）机制通过海绵 miR-454-3p 抑制乳腺癌细胞增殖和迁移，表明靶向 MIR17HG 可能是乳腺癌的可行治疗候选者。

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