CDX2 inhibits pancreatic adenocarcinoma cell proliferation via promoting tumor suppressor miR-615-5p.
CDX2 has recently been identified as a prognostic marker for pancreatic adenocarcinoma. However, the role and mechanism of CDX2 in progression of pancreatic adenocarcinoma are still elusive. In this study, we observed that CDX2 expression was much lower in mouse pancreatic adenocarcinoma tissues and pancreatic cancer cells. A network integrated by ChIPBase platform hinted that miR-615-5p, a most newly discovered tumor suppressor, was probably bound by CDX2 in the promoter region. Chromatin immunoprecipitation (ChIP)-qPCR assay showed that CDX2 exhibited a high capacity of binding to miR-615-5p promoter region compared to the negative control. Real-time PCR and western blotting analyses revealed that CDX2 overexpression caused inflation of miR-615-5p and depression of insulin-like growth factor 2 (IGF2), a direct target of miR-615-5p. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and EdU approaches showed that CDX2 overexpression markedly suppressed pancreatic adenocarcinoma cell proliferation. CDX2 small interfering RNA (siRNA) transfection showed an opposite effect on gene expression and cell proliferation to that of CDX2 overexpression. Collectively, CDX2 inhibited pancreatic adenocarcinoma cell proliferation via promoting tumor suppressor miR-615-5p. Our findings suggested a potential molecular target for pancreatic adenocarcinoma therapy.
Department of Gastroenterology, The Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, People's Republic of China.
Yuanyuan
Y
Jiang
Department of Gastroenterology, The Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, People's Republic of China.
Yan
Y
Zhang
Department of Gastroenterology, The Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, People's Republic of China.
Fuqing
F
Li
Department of Gastroenterology, The Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, People's Republic of China.
Xiaolin
X
Du
Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Eastern Road, Erqi District, Zhengzhou, 450052, People's Republic of China. jinpingzhang126@163.com.
Jinping
J
Zhang
D020413:3' Untranslated Regions; D000818:Animals; D000071616:CDX2 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D047368:Tumor Burden
D020413:3' Untranslated Regions; D000071616:CDX2 Transcription Factor; C035170:IGF2 protein, human; C534344:MIRN615 microRNA, human; D035683:MicroRNAs; D007335:Insulin-Like Growth Factor II
Caudal-type homeobox 2 (CDX2); Insulin-like growth factor 2 (IGF2); Pancreatic adenocarcinoma; Proliferation; miR-615-5p