Xiao Jie, Peng Feng, Yu Chao, Wang Min, Li Xu, Li Zhipeng, Jiang Jianxin, Sun Chengyi
Department of Hepatobiliary Surgery, Affiliated Hospital of Guiyang Medical College Guiyang 550004, Guizhou Province, China.
Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Hazhong University of Science and Technology Wuhan 430074, Hubei Province, China.
Int J Clin Exp Pathol. 2014 Oct 15;7(11):7442-50. eCollection 2014.
We intended to investigate the role of microRNA 137 (miR-137) in regulating pancreatic cancer cells' growth in vitro and tumor development in vivo.
QTR-PCR was used to examine the expression of miR-137 in pancreatic cancer cell lines and tumor cells from human patients. Lentivirual vector containing miR-137 mimic was used to overexpress miR-137 in PANC-1 and MIA PaCa-2 cells. The effects of overexpressing miR-137 on pancreatic cancer cell invasion and chemo-sensitivity to 5-fluorouracil (5-FU) were examined by cell migration and survival essays in vitro. The molecular target of miR-137, pleiotropic growth factor (PTN), was down-regulated by siRNA to examine its effects on cancer cell invasion. MIA PaCa-2 cells with endogenously overexpressed miR-137 were transplanted into null mice to examine tumor growth in vivo.
We found miR-137 was markedly underexpressed in both pancreatic cancer cell lines and tumor cells from patients. In cancer cells, transfection of lentivirus containing miR-137 mimic was able to markedly upregulate endogenous expression of miR-137, inhibited cancer cell invasion and increased sensitivities to chemotherapy reagent 5-FU. PTN was significantly down-regulated by overexpressing miR-137 in pancreatic cancer cells, and knocking down PTN was effective to rescue the reduced cancer cell invasion ability caused by miR-137 overexpression. More importantly, overexpressing miR-137 led to significant inhibition on tumor formation, including reductions in tumor weight and tumor size in vivo.
Our study demonstrated that miR-137 played an important role in pancreatic cancer development. It may become a new therapeutic target for gene therapy in patients suffered from pancreatic cancer.
我们旨在研究微小RNA 137（miR - 137）在体外调节胰腺癌细胞生长及体内肿瘤发展中的作用。
采用定量逆转录聚合酶链反应（QTR - PCR）检测miR - 137在胰腺癌细胞系及人类患者肿瘤细胞中的表达。使用携带miR - 137模拟物的慢病毒载体在PANC - 1和MIA PaCa - 2细胞中过表达miR - 137。通过体外细胞迁移和存活实验检测过表达miR - 137对胰腺癌细胞侵袭及对5 - 氟尿嘧啶（5 - FU）化疗敏感性的影响。通过小干扰RNA（siRNA）下调miR - 137的分子靶点多效生长因子（PTN），以检测其对癌细胞侵袭的影响。将内源性过表达miR - 137的MIA PaCa - 2细胞移植到裸鼠体内，检测体内肿瘤生长情况。
我们发现miR - 137在胰腺癌细胞系及患者肿瘤细胞中均明显低表达。在癌细胞中，转染携带miR - 137模拟物的慢病毒能够显著上调miR - 137的内源性表达，抑制癌细胞侵袭并增加对化疗药物5 - FU的敏感性。在胰腺癌细胞中过表达miR - 137可显著下调PTN，敲低PTN可有效挽救因miR - 137过表达导致的癌细胞侵袭能力降低。更重要的是，过表达miR - 137导致肿瘤形成显著受抑制，包括体内肿瘤重量和肿瘤大小的减小。
我们的研究表明miR - 137在胰腺癌发展中起重要作用。它可能成为胰腺癌患者基因治疗的新靶点。
