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敲低长链非编码 RNA CCAT1 通过下调胃癌中的 Bmi-1 抑制细胞生长、侵袭和腹膜转移。

Knockdown of long noncoding RNA CCAT1 inhibits cell growth, invasion and peritoneal metastasis via downregulation of Bmi-1 in gastric cancer.

机构信息

Department of Medical Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.

出版信息

Neoplasma. 2018 Sep 19;65(5):736-744. doi: 10.4149/neo_2018_171206N801. Epub 2018 Jun 17.

DOI:10.4149/neo_2018_171206N801
PMID:29940756
Abstract

Long noncoding RNA colon cancer-associated transcript 1 (lncRNA CCAT1) is highly expressed in gastric cancer (GC) tissues compared with normal counterparts and CCAT1 upregulation can promote proliferation and migration of GC cells in vitro. B-cell specific moloney leukemia virus insertion site 1 (Bmi-1) expression is positively correlated with tumor progression. The present study aimed to investigate the biological functions of CCAT1 and the relationships between CCAT1 and Bmi-1 in GC progression. In the present study, CCAT1 was knocked down by specific shRNA transfection in two human GC cell lines (MGC-803 and SGC-7901). The effects of CCAT1 knockdown on GC cell proliferation, cell cycle, migration and invasion were investigated in vitro. The effect of CCAT1 knockdown on peritoneal metastasis was assessed in nude mice. Bmi-1 expression levels were examined both in vitro and in vivo. The results showed that CCAT1 knockdown markedly inhibited cell proliferation, migration and invasion, arrested the cell cycle at G0/G1 phase in vitro, and inhibited peritoneal metastasis in nude mice, along with the downregulation of Bmi-1. Taken together, CCAT1 is functionally involved in growth and metastasis of GC cells and it may be a potential target for GC therapy.

摘要

长链非编码 RNA 结肠癌相关转录本 1(lncRNA CCAT1)在胃癌(GC)组织中的表达明显高于正常组织,CCAT1 的上调可促进 GC 细胞在体外的增殖和迁移。B 细胞特异性莫洛尼白血病病毒插入位点 1(Bmi-1)的表达与肿瘤进展呈正相关。本研究旨在探讨 CCAT1 的生物学功能以及 CCAT1 与 Bmi-1 在 GC 进展中的关系。在本研究中,通过特异性 shRNA 转染在两种人 GC 细胞系(MGC-803 和 SGC-7901)中敲低 CCAT1。在体外研究了 CCAT1 敲低对 GC 细胞增殖、细胞周期、迁移和侵袭的影响。在裸鼠中评估了 CCAT1 敲低对腹膜转移的影响。在体外和体内检查了 Bmi-1 的表达水平。结果表明,CCAT1 敲低显著抑制细胞增殖、迁移和侵袭,体外将细胞周期阻滞在 G0/G1 期,并抑制裸鼠的腹膜转移,同时下调 Bmi-1。总之,CCAT1 参与 GC 细胞的生长和转移,可能是 GC 治疗的潜在靶点。

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