The First Department of General Surgery, Affiliated Hospital of Chengde Medical College, Chengde, Hebei, 067000, PR China.
The First Department of Gynecology, The Affiliated Hospital of Chengde Medical College, Chengde, Hebei, 067000, PR China.
Biochem Biophys Res Commun. 2019 May 28;513(2):465-471. doi: 10.1016/j.bbrc.2019.03.125. Epub 2019 Apr 6.
Cholangiocarcinoma (CCA) is the most usual malignancy of biliary tract, possessing a relatively low overall survival rate due to limited treatment options. Recently, long non-coding RNAs (lncRNAs) have been testified to have marked regulatory impacts on human cancers. The purpose of this paper is to explore the potent regulation mechanism of LINC01061 involved in CCA. Firstly, it was observed that LINC01061 expression was heightened in CCA cell lines, whose knockdown suppressed cell proliferation, induced cell apoptosis and restrained cell migration. Besides, LINC01061 existing in the cytoplasm of CCA cells interacted with miR-612. Moreover, subsequent experiments affirmed that LINC01061 regulated SEMA4D expression by acting as a competing endogenous RNA (ceRNA) of miR-612. At last, rescue assays validated that SEMA4D overexpression restored the repression caused by LINC01061 silence on the biological activities of CCA containing cell proliferation, apoptosis and migration. To sum up, our present exploration demonstrated that LINC01061 sponges miR-612 so as to upregulate SEMA4D expression for the progression of CCA, suggesting an optional promising and effective target for the therapy of patients with CCA.
胆管癌（CCA）是胆道最常见的恶性肿瘤，由于治疗选择有限，总体生存率相对较低。最近，长非编码 RNA（lncRNA）已被证明对人类癌症具有显著的调控作用。本文旨在探讨 LINC01061 参与 CCA 的潜在调控机制。首先，观察到 LINC01061 在 CCA 细胞系中的表达升高，其敲低抑制细胞增殖、诱导细胞凋亡并抑制细胞迁移。此外，CCA 细胞细胞质中的 LINC01061 与 miR-612 相互作用。此外，后续实验证实 LINC01061 通过作为 miR-612 的竞争性内源性 RNA（ceRNA）来调节 SEMA4D 的表达。最后，挽救实验验证了 SEMA4D 的过表达恢复了 LINC01061 沉默对包含细胞增殖、凋亡和迁移的 CCA 生物学活性的抑制作用。总之，我们目前的研究表明，LINC01061 作为 miR-612 的海绵，从而上调 SEMA4D 的表达，促进 CCA 的进展，为 CCA 患者的治疗提供了一个有希望的有效靶点。
