Department of Medical Oncology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian, China.
Eur Rev Med Pharmacol Sci. 2020 Feb;24(3):1098-1107. doi: 10.26355/eurrev_202002_20160.
Abnormal expression of micro ribonucleic acids (miRNAs) has become an important marker of cancer. However, the exact molecular mechanisms of miRNAs were not very clear. Here, we decided to investigate the miR-19 effect and molecular mechanism on pancreatic cancer, which was blank until now.
Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was applied for testing miR-19 and gene of phosphate and tensin homolog deleted on chromosome ten (PTEN) expression. Western blot was used for detecting the protein expression. Methyl thiazolyl tetrazolium (MTT) assay and transwell assay were carried out to measure cell proliferation, invasion, and migration.
We showed that miR-19 expression was increased in cancerous tissues and was associated with the survival of patients, tumor node metastasis (TNM) stage, tumor size, and lymph node metastasis. MiR-19 mimic enhanced cell proliferation, invasion, and migration, while suppressing miR-19 cell progression was suppressed. With the help of TargetScanHuman and luciferase reporter assay, we verified PTEN as a specific target of miR-19. Moreover, PTEN expression was reduced by miR-19 mimic and was increased by miR-19 inhibitor. We next found that PTEN was elevated in cancerous tissues and its expression was negatively correlated with miR-19 expression. Furthermore, miR-19 regulated cell progression via activating phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/AKT) signaling pathway.
We demonstrated that miR-19 facilitated cell progression through modulating PI3K/AKT signaling pathway by targeting PTEN, which provided a potential therapeutic target for pancreatic cancer patients.
微小核糖核酸（miRNAs）的异常表达已成为癌症的重要标志物。然而，miRNAs 的确切分子机制尚不清楚。在这里，我们决定研究 miR-19 对胰腺癌的影响及其分子机制，这方面的研究至今仍是空白。
采用实时定量聚合酶链反应（qRT-PCR）分析检测 miR-19 和磷酸酶及张力蛋白同源物基因缺失于染色体 10 号（PTEN）的表达。采用蛋白质印迹法检测蛋白表达。噻唑蓝（MTT）比色法和 Transwell 小室法检测细胞增殖、侵袭和迁移。
我们发现，miR-19 在癌组织中表达增加，与患者的生存、肿瘤淋巴结转移（TNM）分期、肿瘤大小和淋巴结转移有关。miR-19 模拟物增强细胞增殖、侵袭和迁移，而抑制 miR-19 则抑制细胞进展。借助 TargetScanHuman 和荧光素酶报告基因检测，我们验证了 PTEN 是 miR-19 的一个特异性靶基因。此外，miR-19 模拟物降低了 PTEN 的表达，而 miR-19 抑制剂则增加了其表达。我们还发现，PTEN 在癌组织中表达升高，其表达与 miR-19 的表达呈负相关。此外，miR-19 通过激活磷脂酰肌醇 3-羟激酶/蛋白激酶 B（PI3K/AKT）信号通路来调节细胞的进展。
我们证明 miR-19 通过靶向 PTEN 调节 PI3K/AKT 信号通路促进细胞进展，为胰腺癌患者提供了一个潜在的治疗靶点。
