Breast cancer (BC) is the leading cause of cancer-related death in women worldwide and one of the most prevalent malignancy. In recent years, increasing evidence had illuminated that long noncoding RNAs (lncRNAs) serve as critical factors in multiple tumor progression, including BC. Emerging references had indicated that the lncRNA H19 acts as significant roles in tumor progression and epithelial-mesenchymal transition (EMT). However, the underlying molecular mechanisms and biological roles of H19 in BC invasion, metastasis and EMT are still unclear. In this study, it was detected that the expression level of H19 was increased in BC paclitaxel-resistant (PR) cells subline (MCF-7/PR) in comparison with MCF-7 parental cells. In vitro, there were demonstrated that H19 overexpression promoted BC cells proliferation, metastasis, invasion and EMT procedures, and suppressed cells apoptosis. Whereas, H19 suppression resulted in the contrary biological effects. Besides, bioinformatics tools and dual-luciferase reporters assays indicated that miR-340-3p could act as a potential target gene of H19, the underlying mechanism studies proved that H19 could act as a competing endogenous RNA (ceRNA) via competitively binding miR-340-3p to promote BC cell proliferation, metastasis and EMT by regulating tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) and potentiate the Wnt/β-catenin signaling in BC cells. In summary, our findings demonstrated that H19 could act as a ceRNA in BC progression, metastasis and EMT through modulating miR-340-3p/YWHAZ axis and activating the canonical Wnt/β-catenin signaling pathway, indicating that H19 might act as an underlying therapeutic target and prognostic biomarker for BC therapy.

中文翻译：

---

长链非编码RNA H19作为miR-340-3p海绵通过调节紫杉醇耐药乳腺癌细胞中YWHAZ的表达促进上皮-间质转化

乳腺癌 (BC) 是全球女性癌症相关死亡的主要原因，也是最普遍的恶性肿瘤之一。近年来，越来越多的证据表明，长链非编码 RNA (lncRNA) 是多种肿瘤进展的关键因素，包括 BC。新出现的参考文献表明 lncRNA H19 在肿瘤进展和上皮间质转化 (EMT) 中发挥着重要作用。然而，H19 在 BC 侵袭、转移和 EMT 中的潜在分子机制和生物学作用仍不清楚。在本研究中，检测到与 MCF-7 亲本细胞相比，BC 紫杉醇抗性 (PR) 细胞亚系 (MCF-7/PR) 中 H19 的表达水平增加。体外研究表明，H19 过表达促进 BC 细胞增殖、转移、侵袭和 EMT 程序，并抑制细胞凋亡。然而，H19 抑制导致相反的生物学效应。此外，生物信息学工具和双荧光素酶报告基因检测表明 miR-340-3p 可以作为 H19 的潜在靶基因，潜在机制研究证明 H19 可以通过竞争性结合 miR-340 作为竞争性内源 RNA（ceRNA） -3p 通过调节酪氨酸 3-单加氧酶/色氨酸 5-单加氧酶激活蛋白 zeta (YWHAZ) 来促进 BC 细胞增殖、转移和 EMT，并增强 BC 细胞中的 Wnt/β-连环蛋白信号传导。总之，我们的研究结果表明，H19 可以通过调节 miR-340-3p/YWHAZ 轴和激活经典 Wnt/β-catenin 信号通路在 BC 进展、转移和 EMT 中充当 ceRNA，