title: Deregulation of MicroRNA-375 inhibits cancer proliferation migration and chemosensitivity in pancreatic cancer through the association of HOXB3.
abstract: BACKGROUND
  The expression pattern and regulatory effect of microRNA-375 (miR-375) in human pancreatic cancer was explored.
  
  
  METHODS
  Gene expression of miR-375 was compared between pancreatic tumors and non-tumorous pancreatic tissues, as well as pancreatic cancer cell lines and normal epithelial cells. MiR-375 was downregulated in pancreatic cancer cell lines, Capan-1 and PANC-1 cells, to assess possible tumor suppressive effects on cancer proliferation, migration, cisplatin chemosensitivity and in vivo growth of tumor explant. The regulation of miR-375 on its target gene, homeobox B3 (HOXB3) gene, was assessed though luciferase activity assay and qRT-PCR. HOXB3 was also downregulated in Capan-1 and PANC-1 cells to assess its functional correlation with miR-375 on cancer regulation.
  
  
  RESULTS
  MiR-375 was upregulated in pancreatic tumors and pancreatic cancer cell lines. MiR-375 downregulation had tumor suppressive effects in Capan-1 and PANC-1 cells by reducing cancer proliferation & migration, increasing cisplatin sensitivity and inhibiting in vivo tumor explant growth. HOXB3 was directly bound by miR-375, and was negatively regulated by miR-375 in pancreatic cancer cells. Subsequent HOXB3 downregulation reversed the suppression of miR-375 downregulation on cancer proliferation, migration and cisplatin chemosensitivity in pancreatic cancer.
  
  
  CONCLUSIONS
  MiR-375 is an oncogene in pancreatic cancer. Deregulation of miR-375 is inhibitory to the development of pancreatic cancer, and reversely regulated by HOXB3.
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai Changzheng Hospital Shanghai 200003, China.
authors.forename: Dejun
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai Changzheng Hospital Shanghai 200003, China.
authors.forename: Ronglin
authors.initials: R
authors.lastname: Yan
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai Changzheng Hospital Shanghai 200003, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai Changzheng Hospital Shanghai 200003, China.
authors.forename: Zhenxin
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai Changzheng Hospital Shanghai 200003, China.
authors.forename: Changming
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai Changzheng Hospital Shanghai 200003, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai Changhai Hospital Shanghai 200433, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
keywords: HOXB3; Pancreatic cancer; cancer migration; cancer proliferation; cisplatin; miR-375