Department of Ultrasound, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, People's Republic of China.
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang, Liaoning, People's Republic of China.
Mol Cell Biochem. 2020 Apr;467(1-2):95-105. doi: 10.1007/s11010-020-03704-y. Epub 2020 Feb 24.
Ovarian cancer has the highest mortality in gynecologic malignancies. LncRNA BLACAT1 serves crucial functions in various cancers, but its role in ovarian cancer has not been investigated. In this article, our team explored the role and the potential regulatory mechanism of BLACAT1 in ovarian cancer. Quantitative RT-PCR showed that BLACAT1 was aberrantly up-regulated in ovarian cancer tissues compared with normal tissues. In vitro, BLACAT1 knockdown induced cell cycle arrest and inhibited the proliferation, migration and invasion of ovarian cancer cells using flow cytometry, MTT and EdU assays, wound healing assay and transwell assay, respectively. Luciferase assay verified the binding relationship between microRNA-519d-3p and lncRNA BLACAT1, and BLACAT1 negatively regulated the expression of miR-519d-3p. We also found that miR-519d-3p overexpression could inhibit ovarian cancer cells proliferation, migration and invasion. Further, Western blot demonstrated that the expression of RPS15A and nuclear β-catenin expression was markedly reduced by BLACAT1 knockdown, and cytoplasmic β-catenin level was not obviously affected. In vivo, BLACAT1 knockdown inhibited the tumor growth, and immunohistochemistry showed that ki67 expression was decreased by BLACAT1 suppression. Inhibition of BLACAT1 was sufficient to down-regulate the expression of RPS15A and nuclear β-catenin but did not cause an obvious change in cytoplasmic β-catenin expression. Taken together, BLACAT1 knockdown inhibited the progression of ovarian cancer by suppressing the Wnt/β-catenin signaling pathway via regulating miR-519d-3p. Our work provided a proper understanding of the critical roles of BLACAT1 in ovarian cancer.
卵巢癌是妇科恶性肿瘤中死亡率最高的癌症。LncRNA BLACAT1 在各种癌症中发挥着关键作用，但它在卵巢癌中的作用尚未被研究。在本文中，我们的团队探讨了 BLACAT1 在卵巢癌中的作用及其潜在的调节机制。定量 RT-PCR 显示，BLACAT1 在卵巢癌组织中的表达异常上调，与正常组织相比。在体外，BLACAT1 敲低通过流式细胞术、MTT 和 EdU 测定、划痕愈合测定和 Transwell 测定分别诱导细胞周期停滞，并抑制卵巢癌细胞的增殖、迁移和侵袭。荧光素酶测定验证了 microRNA-519d-3p 和 lncRNA BLACAT1 之间的结合关系，并且 BLACAT1 负调控 miR-519d-3p 的表达。我们还发现 miR-519d-3p 的过表达可以抑制卵巢癌细胞的增殖、迁移和侵袭。进一步，Western blot 表明，BLACAT1 敲低显著降低了 RPS15A 的表达和核β-catenin 的表达，而细胞质β-catenin 水平没有明显影响。在体内，BLACAT1 敲低抑制肿瘤生长，免疫组化显示 BLACAT1 抑制后 ki67 表达降低。BLACAT1 的抑制足以下调 RPS15A 和核β-catenin 的表达，但不会导致细胞质β-catenin 表达明显变化。总之，BLACAT1 敲低通过调节 miR-519d-3p 抑制 Wnt/β-catenin 信号通路抑制卵巢癌的进展。我们的工作为 BLACAT1 在卵巢癌中的关键作用提供了适当的认识。
