Department of Hepatobiliary Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, China.
Ganzhou Key Laboratory of Hepatocellular carcinoma, The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, China.
Biomed Res Int. 2023 Jan 13;2023:7518744. doi: 10.1155/2023/7518744. eCollection 2023.
Pancreatic cancer remains a deadly solid tumor with worst survival, and a better understanding of the mechanisms of carcinogenesis of pancreatic cancer is critical to promote the survival of patients with pancreatic cancer. qPCR and western blot assay were used to determine the expression of SPRR3 in pancreatic cancer. Anchorage-independent growth ability, BrdU labeling, Transwell assay, and in vivo experiment were used to examine the functions of SPRR3 in aggressiveness of pancreatic cancer. Luciferase reporter assay, nucleoplasmic-separation technique, qPCR, and western blot assay were used to investigate the mechanism of SPRR3 regulating aggressiveness of pancreatic cancer. Our results showed that SPRR3 was significantly increased in pancreatic cancer, which resulted in poor survival for patients with pancreatic cancer. Further analysis showed that overexpression of SPRR3 contributed to anchorage-independent growth ability, growth rate, and invasion ability of pancreatic cancer cells. While, knockdown of SPRR3 showed the reverse results. Mechanistically, overexpression of SPRR3 can promote the transcription of NF-B pathway, nuclear accumulation of p65, and mRNA levels of NF-B pathway downstream genes. But, knockdown of SPRR3 induced the reverse results. The above findings clarified the important roles of SPRR3 in the progression of pancreatic cancer through NF-B pathway. And targeting SPRR3 might be an effective strategy to therapy pancreatic cancer.
胰腺癌仍然是一种致命的实体肿瘤，存活率最差，因此深入了解胰腺癌的致癌机制对于提高胰腺癌患者的生存率至关重要。我们使用 qPCR 和 Western blot 检测来确定 SPRR3 在胰腺癌中的表达。我们使用非依赖性生长能力测定、BrdU 标记、Transwell 测定和体内实验来研究 SPRR3 在胰腺癌侵袭性中的功能。我们使用荧光素酶报告基因检测、核质分离技术、qPCR 和 Western blot 检测来研究 SPRR3 调节胰腺癌侵袭性的机制。我们的结果表明，SPRR3 在胰腺癌中显著增加，导致胰腺癌患者的生存状况较差。进一步的分析表明，过表达 SPRR3 促进了胰腺癌细胞的非依赖性生长能力、生长速度和侵袭能力。而敲低 SPRR3 则显示出相反的结果。从机制上讲，过表达 SPRR3 可以促进 NF-κB 通路的转录、p65 的核积累以及 NF-κB 通路下游基因的 mRNA 水平。但是，敲低 SPRR3 则诱导了相反的结果。上述发现阐明了 SPRR3 通过 NF-κB 通路在胰腺癌进展中的重要作用。因此，靶向 SPRR3 可能是治疗胰腺癌的有效策略。
