MicroRNA Expression Profiling of Pancreatic Cancer Cell Line L3.6p1 Following B7-H4 Knockdown

Background/Aims: Co-stimulating molecule B7-H4 regulates T cell-mediated immune responses, participates in tumor immune escape, and promotes the proliferation and metastasis of pancreatic cancer cells. However, the specific mechanisms are unclear. MicroRNAs (miRNAs) participated in the pathogenesis and progression of cancer. Methods: In this study, a microarray technique was used to screen B7-H4-related differentially expressed miRNAs in a pancreatic cancer cell line find those associated with pancreatic cancer. Using a miRCURYTM LNA Array approach, we compared the miRNA expression profiles of L3.6p1 pancreatic cancer cells transfected with B7-H4 siRNA for 72 h with those transfected with non-target siRNAs. Results: B7-H4 siRNA significantly up-regulated 57 miRNAs and down-regulated 14 miRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis of predicted miRNA targets showed that these genes were mainly involved in protein binding, pathways in cancer, mitogen-activated protein kinase (MAPK) signaling pathway, and phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling pathway. Conclusions: This is the first description of target genes of B7-H4, showing that miRNAs participate in the B7-H4 mediated regulation of oncogenicity and pathogenesis of pancreatic cancer. These results may help us better understand the role of B7-H4 in the progression of pancreatic cancer and its possible mechanisms. We also provide novel biomarkers for potential treatments of pancreatic cancer.

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ERK signaling pathway may induce gemcitabine chemoresistance in pancreatic cancer cell line SW1990 by regulating the expression of mdr-1 and RRM1 gene

The Chinese-German Journal of Clinical Oncology ◽

10.1007/s10330-008-0145-5 ◽

2009 ◽

Vol 8 (1) ◽

pp. 37-41 ◽

Cited By ~ 1

Author(s):

Denglin Chen ◽

Derong Xie ◽

Shuangshuang Guo ◽

Qiong Yang ◽

Zhimin Jiang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cell Line ◽

Signaling Pathway ◽

Cancer Cell ◽

Pancreatic Cancer Cell ◽

Pancreatic Cancer Cell Line ◽

Cancer Cell Line ◽

Erk Signaling ◽

Mdr 1

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Activation of GLP-1 receptor enhances the chemosensitivity of pancreatic cancer cells

Journal of Molecular Endocrinology ◽

10.1530/jme-19-0186 ◽

2020 ◽

Vol 64 (2) ◽

pp. 103-113

Author(s):

He-jun Zhao ◽

Xia Jiang ◽

Li-juan Hu ◽

Lei Yang ◽

Lian-dong Deng ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Cell Line ◽

Pancreatic Cancer Cell ◽

Pancreatic Cancer Cell Line ◽

Cancer Cell Line ◽

Human Pancreatic Cancer ◽

Pancreatic Cancer Cells

This study aimed to determine whether and how the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide affects the chemoresistance and chemosensitivity of pancreatic cancer cells to gemcitabine in vitro and in vivo. The GLP-1R and protein kinase A (PKA) levels were compared between the human pancreatic cancer cell line PANC-1 and the gemcitabine-resistant cell line PANC-GR. The in vitro effects of liraglutide on the cell proliferation and apoptosis as well as the nuclear factor-kappa B NF-κB expression levels of PANC-GR cells were evaluated. In addition, a mouse xenograft model of human pancreatic cancer was established by s.c. injection of PANC-1 cells, and the effects of liraglutide on the chemosensitivity were evaluated in vitro and in vivo. In contrast to PANC-1 cells, PANC-GR cells exhibited lower expression levels of GLP-1R and PKA. Incubation with liraglutide dose dependently inhibited the growth, promoted the apoptosis, and increased the expression of GLP-1R and PKA of PANC-GR cells. Similar effects of liraglutide were observed in another human pancreatic cancer cell line MiaPaCa-2/MiaPaCa-2-GR. Either the GLP-1R antagonist Ex-9, the PKA inhibitor H89, or the NF-κB activator lipopolysaccharide (LPS) could abolish the antiproliferative and proapoptotic activities of liraglutide. Additionally, each of these agents could reverse the expression of NF-κB and ABCG2, which was decreased by liraglutide treatment. Furthermore, liraglutide treatment increased the chemosensitivity of pancreatic cancer cells to gemcitabine, as evidenced by in vitro and in vivo experiments. Thus, GLP-1R agonists are safe and beneficial for patients complicated with pancreatic cancer and diabetes, especially for gemcitabine-resistant pancreatic cancer.

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