Hepatobiliary surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
Department of Plastic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
Cell Death Dis. 2021 Sep 22;12(10):859. doi: 10.1038/s41419-021-04123-7.
The lncRNA ZFAS1 plays a carcinogenic regulatory role in many human tumours, but it is rarely reported in pancreatic cancer. We identify the role and molecular mechanisms of ZFAS1 in pancreatic cancer. The expression of ZFAS1, miR-497-5p and HMGA2 in pancreatic cancer tissues was detected by qRT-PCR. Pancreatic cancer data in The Cancer Genome Atlas were also included in this study. CCK8, EdU, transwell and scratch wound assays were used to investigate the biological effects of ZFAS1 in pancreatic cancer cells. MS2-RIP, RNA pull-down, RNA-ChIP and luciferase reporter assays were used to clarify the molecular biological mechanisms of ZFAS1 in pancreatic cancer. The role of ZFAS1 in vivo was also confirmed via xenograft experiments. ZFAS1 was overexpressed in pancreatic cancer tissues. ZFAS1 promoted the growth and metastasis of pancreatic cancer cells, and miR-497-5p acted as a tumour suppressor gene in pancreatic cancer by targeting HMGA2. We also demonstrated that ZFAS1 exerts its effects by promoting HMGA2 expression through decoying miR-497-5p. We also found that ZFAS1 promoted the progression of pancreatic cancer in vivo by modulating the miR-497-5p/HMGA2 axis. In conclusion, this study revealed a new role for and the molecular mechanisms of ZFAS1 in pancreatic cancer, identifying ZFAS1 as a novel target for the diagnosis and treatment of pancreatic cancer.
长链非编码 RNA ZFAS1 在许多人类肿瘤中发挥致癌调节作用，但在胰腺癌中很少有报道。我们确定了 ZFAS1 在胰腺癌中的作用和分子机制。通过 qRT-PCR 检测胰腺癌组织中 ZFAS1、miR-497-5p 和 HMGA2 的表达。本研究还纳入了癌症基因组图谱中的胰腺癌数据。通过 CCK8、EdU、transwell 和划痕实验研究 ZFAS1 对胰腺癌细胞的生物学影响。MS2-RIP、RNA 下拉、RNA-ChIP 和荧光素酶报告基因实验用于阐明 ZFAS1 在胰腺癌中的分子生物学机制。还通过异种移植实验证实了 ZFAS1 在体内的作用。ZFAS1 在胰腺癌组织中过表达。ZFAS1 促进了胰腺癌细胞的生长和转移，miR-497-5p 通过靶向 HMGA2 作为胰腺癌中的肿瘤抑制基因发挥作用。我们还表明，ZFAS1 通过诱饵 miR-497-5p 促进 HMGA2 表达来发挥其作用。我们还发现，ZFAS1 通过调节 miR-497-5p/HMGA2 轴在体内促进了胰腺癌的进展。总之，本研究揭示了 ZFAS1 在胰腺癌中的新作用和分子机制，将 ZFAS1 鉴定为诊断和治疗胰腺癌的新靶点。
