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微小RNA-193b直接靶向抑制微管相关蛋白1(STMN1)基因和尿激酶型纤溶酶原激活剂(uPA)基因,并抑制胰腺癌的肿瘤生长和转移。

miR-193b directly targets STMN1 and uPA genes and suppresses tumor growth and metastasis in pancreatic cancer.

作者信息

Li Jian, Kong Fujiao, Wu Kemin, Song Kun, He Jianfeng, Sun Weijia

机构信息

Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

出版信息

Mol Med Rep. 2014 Nov;10(5):2613-20. doi: 10.3892/mmr.2014.2558. Epub 2014 Sep 11.

DOI:10.3892/mmr.2014.2558
PMID:25215905
Abstract

Pancreatic cancer has the poorest prognosis among all cancer types, due to its late diagnosis and the lack of effective therapies. Therefore, identification of novel gene targets, which are differentially expressed in pancreatic cancer and functionally involved in the malignant phenotype, is critical to achieve early diagnosis and develop effective therapeutic strategies. microRNAs (miRNAs) are small non-coding RNAs, which negatively regulate the expression of their targets. Due to their various targets, miRNAs play a key role in a number of physiological processes and in oncogenesis. Therefore, investigating the role of miRNAs in tumor may contribute to the development of new diagnostic and therapeutic tools for various types of cancer, including pancreatic cancer. Here, we investigated the role of miR-193b in pancreatic cancer. Our data showed that the expression of miR-193b is markedly decreased in pancreatic cancer tissues compared to adjacent healthy tissues. The Panc-1 cell line transfected with the miR‑193b exhibited significantly decreased proliferative, migratory, and invasive ability compared to untransfected cells. Moreover, miR-193b inhibited the expression of stathmin 1 (STMN1) and urokinase-type plasminogen activator (uPA) in Panc-1 cells. These data suggest that miR-193b acts as a tumor suppressor in pancreatic cancer. Therefore, miR-193b may constitute a promising therapeutic agent for the suppression of pancreatic cancer cell growth and metastasis.

摘要

在所有癌症类型中,胰腺癌的预后最差,这归因于其诊断较晚且缺乏有效的治疗方法。因此,鉴定在胰腺癌中差异表达且在恶性表型中发挥功能作用的新基因靶点,对于实现早期诊断和制定有效的治疗策略至关重要。微小RNA(miRNA)是一类小的非编码RNA,它们负向调控其靶标的表达。由于其具有多种靶标,miRNA在许多生理过程和肿瘤发生过程中发挥关键作用。因此,研究miRNA在肿瘤中的作用可能有助于开发针对包括胰腺癌在内的各种癌症的新诊断和治疗工具。在此,我们研究了miR-193b在胰腺癌中的作用。我们的数据显示,与相邻的健康组织相比,miR-193b在胰腺癌组织中的表达明显降低。与未转染的细胞相比,用miR-193b转染的Panc-1细胞系表现出显著降低的增殖、迁移和侵袭能力。此外,miR-193b抑制了Panc-1细胞中1型微管相关蛋白(STMN1)和尿激酶型纤溶酶原激活剂(uPA)的表达。这些数据表明,miR-193b在胰腺癌中起肿瘤抑制作用。因此,miR-193b可能构成一种有前景的治疗剂,用于抑制胰腺癌细胞的生长和转移。

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