title: Downregulation of microRNA-181d had suppressive effect on pancreatic cancer development through inverse regulation of KNAIN2.
abstract: We explored the expression and function of miR-181d (microRNA-181d) in human pancreatic cancer. Quantitative real-time polymerase chain reaction was used to probe miR-181d expression in both pancreatic cancer cell lines and human pancreatic carcinoma. Pancreatic cancer cell lines, PANC-1 and AsPC-1 cells, were engineered to stably downregulate endogenous miR-181d through lentiviral transduction. The mechanistic effects of miR-181d downregulation on pancreatic cancer development were tested by proliferation, migration, fluorouracil chemosensitivity assays in vitro, and explant assay in vivo. Possible miR-181d downstream gene, NKAIN2 (Na+/K+ transporting ATPase interacting 2), was tested by dual-luciferase activity assay and quantitative real-time polymerase chain reaction. Functional involvement of NKAIN2 in miR-181d-regulated pancreatic cancer development was tested by small interfering RNA-mediated NKAIN2 knockdown in miR-181d-downregulated PANC-1 and AsPC-1 cells. MiR-181d was upregulated in both pancreatic cancer cell lines and human pancreatic carcinoma. Lentivirus-induced miR-181d downregulation decreased pancreatic cancer proliferation, migration, and fluorouracil resistance in vitro and inhibited the growth of cancer explant in vivo. NKAIN2 was directly targeted by miR-181d in pancreatic cancer. Small interfering RNA-mediated NKAIN2 knockdown reversed the inhibition of miR-181d downregulation on pancreatic cancer development. MiR-181d is aberrantly overexpressed in pancreatic cancer. Inhibiting miR-181d may suppress pancreatic cancer development, possibly through the inverse regulation on NKAIN2.
authors.affiliation: 1 Department of Nuclear Medicine, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Guopeng
authors.initials: G
authors.lastname: Zhang
authors.affiliation: 2 Department of Oncology, Affiliated Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Dongbo
authors.initials: D
authors.lastname: Liu
authors.affiliation: 2 Department of Oncology, Affiliated Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Guoxian
authors.initials: G
authors.lastname: Long
authors.affiliation: 2 Department of Oncology, Affiliated Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: 2 Department of Oncology, Affiliated Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Qiu
authors.affiliation: 2 Department of Oncology, Affiliated Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Guangyuan
authors.initials: G
authors.lastname: Hu
authors.affiliation: 2 Department of Oncology, Affiliated Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Hu
authors.affiliation: 2 Department of Oncology, Affiliated Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shunfang
authors.initials: S
authors.lastname: Liu
mesh_terms: D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000209:etiology* / Q000517:prevention & control
chemical_list: C540193:MIrn181 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; C460140:NKAIN2 protein, human
keywords: NKAIN2; Pancreatic cancer; fluorouracil; miR-181d; migration; proliferation; xenograft