Sp1-driven up-regulation of miR-19a decreases RHOB and promotes pancreatic cancer

作者：Tan, Yonggang; Yin, Hongzhuan; Zhang, Heying; Fang, Jun; Zheng, Wei; Li, Dan; Li, Yue; Cao, Wei; Sun, Cheng; Liang, Yusi; Zeng, Juan; Zou, Huawei; Fu, Weineng; Yang, Xianghong^*

来源：Oncotarget, 2015, 6(19): 17391-17403.

DOI：10.18632/oncotarget.3975

• pancreatic cancer
• miRNA
• transcription factor
• target gene

Cancer treatment alters microRNA (miRNA) expression, revealing potential therapeutic targets (oncotarget). Here we treated pancreatic cancer (ASPC-1) cells with either recombinant human endostatin (rh-endostatin) or gemcitabine. Then high-throughput sequencing assay was performed to screen for altered miRNAs. Both treatments decreased levels of MiR-19a. We found that miR-19a stimulated cell proliferation, migration, invasion in vitro and tumor growth in vivo. High levels of miR-19a correlated with poor prognosis in patients. Ras homolog family member B (RHOB) was identified as a direct target of miR-19a. Furthermore, RHOB was down-regulated in human pancreatic cancer samples. Restoration of RHOB induced apoptosis, inhibited proliferation and migration of ASPC-1 cells. SP-1 was identified as an upstream transcription factor of miR-19a gene, promoting miR-19a transcription. Rh-endostatin decreased miR-19a expression by down-regulating SP-1. These findings suggest that miR-19a is a potential therapeutic target in pancreatic cancer.

• 出版日期2015-7-10
• 单位中国医科大学