Department of General Surgery, The 960th Hospital of the Chinese people's Liberation Army, Zhoucun District, Zibo.
Department of General Surgery, Chengwu County People's Hospital, Chengwu County, Heze.
Anticancer Drugs. 2021 Aug 1;32(7):681-692. doi: 10.1097/CAD.0000000000001044.
MiRNA is an important regulator of tumorigenesis and tumor progression. MiR-337 expression was increased in pancreatic cancer tissues and it was associated with patients' survival. This study aimed to explore the influence and the potential working mechanism of miR-337 on the malignant behaviors of pancreatic cancer cells. MiR-337 expression was detected by qRT-PCR. The expression levels of STAT3, epithelial-mesenchymal transition-related genes and Wnt/β-Catenin pathway genes were evaluated by qRT-PCR and western blot. Cell counting kit -8 and colony formation assays were conducted to examine the proliferation of AsPC-1 and SW1990 cells. Wound healing and transwell assays were performed to determine the migration and invasion of AsPC-1 and SW1990 cells. The predicted target gene of miR-337 was verified by luciferase reporter assay. The expression of miR-337 was decreased and STAT3 expression was increased in pancreatic cancer tissues as well as tumor cells. Overexpression of miR-337 suppressed proliferation, invasion and migration of AsPC-1 and SW1990 cells. MiR-337 targeted 3'UTR of STAT3 and inhibited STAT3 expression. In addition, exogenous STAT3 partially restored the inhibitory role of miR-337 on proliferation, invasion and migration of AsPC-1 and SW1990 cells. Moreover, miR-337 impeded the expression of Wnt/β-catenin pathway-related genes. Through the saving experiment, we found that the inhibitory effect of miR-337 on AsPC-1 and SW1990 cells was abolished by the addition of LiCl. These outcomes expounded that miR-337 inactivated the Wnt/β-catenin pathway to suppress the malignant behaviors of pancreatic cancer cells through targeting STAT3. This study may provide a novel biomarker for diagnosis and a new therapeutic target for pancreatic cancer treatment.
miRNA 是肿瘤发生和肿瘤进展的重要调节因子。miR-337 在胰腺癌组织中表达增加,与患者的生存相关。本研究旨在探讨 miR-337 对胰腺癌细胞恶性行为的影响及其潜在作用机制。通过 qRT-PCR 检测 miR-337 的表达。通过 qRT-PCR 和 Western blot 评估 STAT3、上皮-间充质转化相关基因和 Wnt/β-连环蛋白通路基因的表达水平。通过细胞计数试剂盒-8 和集落形成实验检测 AsPC-1 和 SW1990 细胞的增殖。通过划痕愈合和 Transwell 实验检测 AsPC-1 和 SW1990 细胞的迁移和侵袭。通过荧光素酶报告基因实验验证 miR-337 的预测靶基因。在胰腺癌组织和肿瘤细胞中,miR-337 的表达降低,STAT3 的表达增加。miR-337 的过表达抑制了 AsPC-1 和 SW1990 细胞的增殖、侵袭和迁移。miR-337 靶向 STAT3 的 3'UTR 并抑制 STAT3 的表达。此外,外源性 STAT3 部分恢复了 miR-337 对 AsPC-1 和 SW1990 细胞增殖、侵袭和迁移的抑制作用。此外,miR-337 抑制了 Wnt/β-连环蛋白通路相关基因的表达。通过挽救实验,我们发现加入 LiCl 可消除 miR-337 对 AsPC-1 和 SW1990 细胞的抑制作用。这些结果表明,miR-337 通过靶向 STAT3 抑制胰腺癌细胞中 Wnt/β-连环蛋白通路的表达,从而抑制胰腺癌细胞的恶性行为。本研究可为胰腺癌的诊断提供新的生物标志物,为胰腺癌的治疗提供新的治疗靶点。