LncRNA BC032020 通过靶向 ZNF451 抑制人胰腺导管腺癌细胞的存活。

LncRNA BC032020 suppresses the survival of human pancreatic ductal adenocarcinoma cells by targeting ZNF451.

机构信息

Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

出版信息

Int J Oncol. 2018 Apr;52(4):1224-1234. doi: 10.3892/ijo.2018.4289. Epub 2018 Feb 28.

Abstract

This study examined the effects of long non‑coding RNA (lncRNA) BC032020 on the development of human pancreatic ductal adenocarcinoma (PDAC), and the potential molecular mechanisms responsible for these effects. The expression of BC032020 was assessed in 20 pairs of PDAC tumor tissues and adjacent normal tissues. The overexpression of BC032020 was enforced in the AsPC‑1 and PANC‑1 cells, and the effects on cell proliferation, cell cycle distribution, cell migration and apoptosis were determined. We also analyzed the functions of zinc finger protein 451 (ZNF451), which shares a gene sequence with two exons of BC032020 and a non‑coding region with another two exons, in PDAC cells. The AsPC‑1 and PANC‑1 cells that overexpressed BC032020 were used to establish a subcutaneous tumor xenograft model in order to examine the effects of BC032020 on tumor growth in vivo. The results revealed that the BC032020 levels in the PDAC tumor tissues were lower than those in the adjacent normal tissues, and ZNF451 expression inversely correlated with the BC032020 levels in the PDAC tumor tissues and cell lines. BC032020 overexpression led to a decrease in ZNF451 expression; it also suppressed the proliferation and migration of the AsPC‑1 and PANC‑1 cells, and induced G1 phase arrest and cell apoptosis. The results of in vivo experiments revealed that BC032020 suppressed tumor growth in a xenograft model by inhibiting ZNF451 expression. Taken together, the findings of this study indicate that BC032020 suppresses the survival of PDAC cells by inhibiting ZNF451 expression.

摘要

这项研究探讨了长非编码 RNA(lncRNA)BC032020 对人胰腺导管腺癌(PDAC)发展的影响,以及这些影响的潜在分子机制。评估了 20 对 PDAC 肿瘤组织和相邻正常组织中的 BC032020 表达。在 AsPC-1 和 PANC-1 细胞中强制过表达 BC032020,并确定对细胞增殖、细胞周期分布、细胞迁移和细胞凋亡的影响。我们还分析了锌指蛋白 451(ZNF451)在 PDAC 细胞中的功能,ZNF451 与 BC032020 的两个外显子共享基因序列,与另外两个外显子共享非编码区域。用过表达 BC032020 的 AsPC-1 和 PANC-1 细胞建立皮下肿瘤异种移植模型,以研究 BC032020 对体内肿瘤生长的影响。结果表明,PDAC 肿瘤组织中的 BC032020 水平低于相邻正常组织,ZNF451 的表达与 PDAC 肿瘤组织和细胞系中的 BC032020 水平呈负相关。BC032020 过表达导致 ZNF451 表达下调;它还抑制了 AsPC-1 和 PANC-1 细胞的增殖和迁移,并诱导 G1 期阻滞和细胞凋亡。体内实验结果表明,BC032020 通过抑制 ZNF451 表达抑制异种移植模型中的肿瘤生长。综上所述,这项研究的结果表明,BC032020 通过抑制 ZNF451 表达抑制 PDAC 细胞的存活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6139/5843399/2fd2f4759e0c/IJO-52-04-1224-g00.jpg

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