HNF-1a promotes pancreatic cancer growth and apoptosis resistance via its target gene PKLR.

Abstract:

:Pancreatic ductal adenocarcinoma is one of the deadliest malignant tumors, and many genes play important roles in its development. The hepatocyte nuclear factor-1a (HNF-1a) gene encodes HNF-1a, which is a transcriptional activator. HNF-1a regulates the tissue-specific expression of multiple genes, especially in pancreatic islet cells and in the liver. However, the role of the HNF-1a gene in the development of pancreatic cancer is still unclear. Here, we used immunohistochemical staining and real-time PCR to analyze HNF-1a expression in pancreatic cancer tissue. Stable cell lines with HNF-1a knockdown or overexpression were established to analyze the role of HNF-1a in pancreatic cancer cell proliferation and apoptosis by colony formation assay and flow cytometry. We also analyzed the L-type pyruvate kinase (PKLR) promoter sequence to identify the regulatory effect of HNF-1a on PKLR transcription and confirmed the HNF-1a binding site in the PKLR promoter via a chromatin immunoprecipitation assay. HNF-1a was found to be overexpressed in pancreatic cancer and promoted proliferation while inhibiting apoptosis in pancreatic cancer cells. PKLR was identified as the downstream target gene of HNF-1a and binding of HNF-1a at two sites in PKLR (-1931/-1926 and -966/-961) regulated PKLR transcription. In conclusion, HNF-1a is overexpressed in pancreatic cancer, and the transcription factor HNF-1a can promote pancreatic cancer growth and apoptosis resistance via its target gene PKLR.

authors

Fan Z,Fan K,Deng S,Gong Y,Qian Y,Huang Q,Yang C,Cheng H,Jin K,Luo G,Liu C,Yu X

doi

10.1093/abbs/gmz169

subject

Has Abstract

pub_date

2020-03-18 00:00:00

pages

241-250

issue

3

eissn

1672-9145

issn

1745-7270

pii

5739839

journal_volume

52

pub_type

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