Jin Yangbing, Weng Yuanchi, Wang Yue, Lin Jiewei, Deng Xiaxing, Shen Baiyong, Zhan Qian, Lu Xiongxiong
Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, People's Republic of China.
Research Institute of Pancreatic Disease, Shanghai Jiaotong University School of Medicine, Shanghai 200025, People's Republic of China.
Onco Targets Ther. 2020 Apr 22;13:3389-3399. doi: 10.2147/OTT.S249662. eCollection 2020.
Pancreatic cancer is an extremely lethal digestive cancer with late diagnosis and poor prognosis. miR-934 has been reported to serve as an oncogene in multiple cancers, such as ovarian cancer and bladder cancer. However, its role in pancreatic cancer remains undiscovered.
The expression data of miR-934 were obtained from the Gene Expression Omnibus database and from our own patient samples. The clinicopathological data and corresponding follow-up data were retrieved from The Cancer Genome Atlas database. CCK8 and colony formation assays were conducted to measure cell proliferation capacity in vitro. Wound healing and transwell assays were performed to detect the migration ability of pancreatic cancer cell.
We found that miR-934 was significantly upregulated in pancreatic tumor samples and cell lines. The expression of miR-934 was related to pathological stages. Upregulated miR-934 was associated with poor prognosis in patients with pancreatic cancer. Mir-934 inhibition reduced, while overexpression promoted, cell proliferation and migration. Mechanically, we found miR-934 could directly bind to 3'-UTR of PROX1 leading to mRNA derogation. Furthermore, increased cell proliferation and migration caused by miR-934 overexpression could be reversed by forced PROX1 expression.
miR-934 is an oncogene in pancreatic cancer and could serve as a prognosis indicator for patients with pancreatic cancer, suggesting that miR-934 is a promising therapeutic target for pancreatic cancer.
胰腺癌是一种极具致死性的消化系统癌症，诊断较晚且预后较差。据报道，miR-934在多种癌症中作为癌基因发挥作用，如卵巢癌和膀胱癌。然而，其在胰腺癌中的作用仍未被发现。
miR-934的表达数据来自基因表达综合数据库以及我们自己的患者样本。临床病理数据和相应的随访数据从癌症基因组图谱数据库中获取。进行CCK8和集落形成试验以体外测量细胞增殖能力。进行伤口愈合试验和Transwell试验以检测胰腺癌细胞的迁移能力。
我们发现miR-934在胰腺肿瘤样本和细胞系中显著上调。miR-934的表达与病理分期相关。miR-934上调与胰腺癌患者的不良预后相关。抑制miR-934可降低细胞增殖和迁移，而其过表达则促进细胞增殖和迁移。机制上，我们发现miR-934可直接结合PROX1的3'-UTR导致mRNA降解。此外，miR-934过表达引起的细胞增殖和迁移增加可通过强制表达PROX1来逆转。
miR-934是胰腺癌中的癌基因，可作为胰腺癌患者的预后指标，提示miR-934是胰腺癌有前景的治疗靶点。
