Department of Anesthesia, the First Affiliated Hospital with Nanjing Medical University, Nanjing, P.R. China.
Eur Rev Med Pharmacol Sci. 2020 Oct;24(20):10462-10471. doi: 10.26355/eurrev_202010_23399.
Cancer susceptibility 19 (CASC19), a crucial lncRNA associated with multiple cancers, has been reported to play a vital role in the progression of human malignant tumors. However, the underlying mechanism of CASC19 in pancreatic cancer (PC) was still unknown. The purpose of this study was to explore the biological and clinical significance of CASC19 in PC.
RT-qPCR assay was adopted to analyze CASC19 expression in PC tissues and cell lines. Furthermore, the correlation between the CASC19 level and the survival rate of PC patients was assessed by Kaplan-Meier analysis. Bioinformatics analysis and Luciferase reporter assay were utilized to confirm the interaction between miR-148b and CASC19 or E2F7. Cell viability, migration, invasion, and apoptosis were analyzed using MTT, transwell, and TUNEL assays.
The results elucidated that CASC19 expression was markedly increased in PC tissues and cell lines. Patients with high expression of CASC19 had a short survival time. Silencing of CASC19 attenuated PC cell proliferation, migration, and invasion. Moreover, we identified that miR-148b was a target of CASC19. CASC19 was negatively correlated with miR-148b and positively correlated with E2F7. The inhibitory effect of CASC19 knockdown on the progression of PC was reversed by the down-regulation of miR-148b or up-regulation of E2F7.
These results demonstrated that CASC19 participated in the development of PC. The CASC19/miR-148b/E2F7 axis might be a new study direction for PC treatment.
癌症易感性 19（CASC19）是一种与多种癌症相关的关键 lncRNA，据报道，它在人类恶性肿瘤的进展中发挥着重要作用。然而，CASC19 在胰腺癌（PC）中的作用机制尚不清楚。本研究旨在探讨 CASC19 在 PC 中的生物学和临床意义。
采用 RT-qPCR 法分析 PC 组织和细胞系中的 CASC19 表达。此外，通过 Kaplan-Meier 分析评估 CASC19 水平与 PC 患者生存率的相关性。利用生物信息学分析和荧光素酶报告实验证实 miR-148b 与 CASC19 或 E2F7 的相互作用。通过 MTT、Transwell 和 TUNEL 测定分析细胞活力、迁移和侵袭以及细胞凋亡。
结果表明，CASC19 在 PC 组织和细胞系中表达明显增加。CASC19 高表达的患者生存时间短。沉默 CASC19 可减弱 PC 细胞的增殖、迁移和侵袭。此外，我们确定 miR-148b 是 CASC19 的靶标。CASC19 与 miR-148b 呈负相关，与 E2F7 呈正相关。下调 miR-148b 或上调 E2F7 可逆转 CASC19 敲低对 PC 进展的抑制作用。
这些结果表明 CASC19 参与了 PC 的发生发展。CASC19/miR-148b/E2F7 轴可能成为 PC 治疗的新研究方向。
