HNF1A inhibition induces the resistance of pancreatic cancer cells to gemcitabine by targeting ABCB1.

ABSTRACT:

Background

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor prognosis, and gemcitabine-based chemotherapy remains an effective option for the majority of PDAC patients. Hepatocyte nuclear factor 1α (HNF1A) is a tumor-suppressor in PDAC, but its role in gemcitabine chemoresistance of PDAC has not been clarified.

Methods

The function of HNF1A in gemcitabine was detected by overexpression and knockdown of HNF1A in vitro and in vitro. The regulatory network between HNF1A and ABCB1 was further demonstrated by luciferase assays, deletion/mutation reporter construct assays and CHIP assays.

Findings

Here, we found that HNF1A expression is significantly associated with gemcitabine sensitivity in PDAC cell lines. Moreover, we identified that HNF1A over

SUBMITTER: Lu Y 

PROVIDER: S-EPMC6606897 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature