长链非编码RNA CASC2通过下调miR-21上调PTEN以抑制胰腺癌细胞转移。
Long non-coding RNA CASC2 upregulates PTEN to suppress pancreatic carcinoma cell metastasis by downregulating miR-21.
作者信息
Zhang Hui, Feng Xielin, Zhang Mingyi, Liu Aixiang, Tian Lang, Bo Wentao, Wang Haiqing, Hu Yong
机构信息
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.
出版信息
Cancer Cell Int. 2019 Jan 16;19:18. doi: 10.1186/s12935-019-0728-y. eCollection 2019.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
背景
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。
方法
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。
结果
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。
结论
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。
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