Department of Pediatrics, The First Hospital of Jilin University, Changchun City, Jilin Province, China.
Eur Rev Med Pharmacol Sci. 2020 Aug;24(16):8367-8376. doi: 10.26355/eurrev_202008_22633.
Cholangiocarcinoma (CCA) is one of the tumors with high malignancy of the liver and bile system, whose development and prognosis mechanisms are still not clear. Here, a preliminary illustration was made on the expression and function of long non-coding RNA (lncRNA) CASC2 and the relevant mechanism of its function.
Expression of CASC2 in CCA tissues and cells were examined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Cell proliferation ability was detected using colony formation and Cell Counting Kit-8 (CCK-8) assays while cell invasion and migration abilities were measured using transwell and Matrigel assays. Using bioinformatic analysis, underlying downstream molecules of CASC2 were predicted and by Dual-Luciferase assay and Western blot.
It was found that CASC2 was expressed at a significantly lower level in CCA tissues and cell lines. The overexpression of CASC2 inhibited QBC939 cell proliferation, invasion and migration when the knockdown of CASC2 accelerated HUCCT1 cell growth and metastasis. Besides, miR-18a was identified as a direct target for CASC2, and SOCS5 as target for miR-18a. Moreover, CASC2 functioned as a sponge of miR-18a to promote the SOCS5 expression, then, slowed down the epithelial-to-mesenchymal transition (EMT) progression.
CASC2 was downregulated in CCA tissues and cells. It could inhibit cell proliferation, invasion, migration and EMT via sponging miR-18a/SOCS5 axis. This might provide a novel target for CCA diagnosis and treatment.
胆管癌（CCA）是肝脏和胆道系统恶性程度较高的肿瘤之一，其发展和预后机制尚不清楚。本研究初步探讨了长链非编码 RNA（lncRNA）CASC2 的表达及其功能机制。
采用实时定量聚合酶链反应（qRT-PCR）检测 CCA 组织和细胞中 CASC2 的表达。采用集落形成和细胞计数试剂盒-8（CCK-8）检测细胞增殖能力，Transwell 和 Matrigel 检测细胞侵袭和迁移能力。通过生物信息学分析预测 CASC2 的下游潜在分子，并通过双荧光素酶报告基因和 Western blot 验证。
研究发现 CASC2 在 CCA 组织和细胞系中的表达水平显著降低。过表达 CASC2 抑制 QBC939 细胞的增殖、侵袭和迁移，而敲低 CASC2 则加速 HUCCT1 细胞的生长和转移。此外，miR-18a 被鉴定为 CASC2 的直接靶标，SOCS5 为 miR-18a 的靶标。CASC2 通过海绵吸附 miR-18a 促进 SOCS5 的表达，从而减缓上皮间质转化（EMT）进程。
CASC2 在 CCA 组织和细胞中表达下调。它可以通过海绵吸附 miR-18a/SOCS5 轴抑制细胞增殖、侵袭、迁移和 EMT，这可能为 CCA 的诊断和治疗提供新的靶点。
