Zhang Hui, Feng Xielin, Zhang Mingyi, Liu Aixiang, Tian Lang, Bo Wentao, Wang Haiqing, Hu Yong
Department of Hepatopancreatobiliary Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, No. 55, Section 4 South Renmin Road, Chengdu, 610041 China.
Cancer Cell Int. 2019 Jan 16;19:18. doi: 10.1186/s12935-019-0728-y. eCollection 2019.
The mechanism of pancreatic cancer metastasis remains poorly understood. Recently, lncRNA CASC2 has been demonstrated to be a tumor suppressor in various types of cancer. This study aimed to explore the mechanism of CASC2 in the regulation of pancreatic cancer metastasis.
The expression levels of CASC2 and miR-21 in pancreatic cells were detected by qRT-PCR. Using specific expression vectors, including mimics or shRNA, the expression levels of CASC2, miR-21 and PTEN in pancreatic cells were altered. The association between CASC2, miR-21 and PTEN was detected. Then, cell migration and invasion were assessed using the transwell assay.
CASC2 expression was downregulated in the pancreatic cancer cell lines CAPAN-1, BxPC-3, JF305, PANC-1 and SW1990 compared with levels in normal human pancreatic HPDE6-C7 cells. CACS2 overexpression inhibited the migration and invasion of PANC-1 cells and significantly inhibited the expression of miR-21 and PTEN. MiR-21 was a direct target of CACS2. The overexpression of miR-21 significantly abolished the antimetastatic effects of CASC2 on PANC-1 cells. Moreover, the downregulation of PTEN significantly abolished the antimetastatic effects of CASC2.
CASC2 functions as a tumor suppressor in pancreatic cancer cells to inhibit tumor cell migration and invasion. Our work revealed a novel regulatory mechanism of the CASC2/miR-21/PTEN axis that may be important in pancreatic cancer.
胰腺癌转移的机制仍未完全清楚。最近，长链非编码RNA CASC2已被证明在多种类型的癌症中是一种肿瘤抑制因子。本研究旨在探讨CASC2在调控胰腺癌转移中的机制。
采用qRT-PCR检测胰腺细胞中CASC2和miR-21的表达水平。使用特定的表达载体，包括模拟物或短发夹RNA，改变胰腺细胞中CASC2、miR-21和PTEN的表达水平。检测CASC2、miR-21和PTEN之间的关联。然后，使用Transwell实验评估细胞迁移和侵袭能力。
与正常人胰腺HPDE6-C7细胞相比，胰腺癌细胞系CAPAN-1、BxPC-3、JF305、PANC-1和SW1990中CASC2表达下调。CACS2过表达抑制了PANC-1细胞的迁移和侵袭，并显著抑制了miR-21和PTEN的表达。miR-21是CACS2的直接靶点。miR-21的过表达显著消除了CASC2对PANC-1细胞的抗转移作用。此外，PTEN的下调显著消除了CASC2的抗转移作用。
CASC2在胰腺癌细胞中作为肿瘤抑制因子发挥作用，抑制肿瘤细胞的迁移和侵袭。我们的研究揭示了CASC2/miR-21/PTEN轴的一种新的调控机制，这可能在胰腺癌中具有重要意义。
