MIR21 Drives Resistance to Heat Shock Protein 90 Inhibition in Cholangiocarcinoma.

ABSTRACT:

Background & aims

Cholangiocarcinomas (CCA) are resistant to chemotherapy, so new therapeutic agents are needed. We performed a screen to identify small-molecule compounds that are active against CCAs. Levels of microRNA 21 (MIR21 or miRNA21) are increased in CCAs. We investigated whether miRNA21 mediates resistance of CCA cells and organoids to HSP90 inhibitors.

Methods

We performed a high-throughput screen of 484 small-molecule compounds to identify those that reduced viability of 6 human CCA cell lines. We tested the effects of HSP90 inhibitors on cells with disruption of the MIR21 gene, cells incubated with MIR21 inhibitors, and stable cell lines with inducible expression of MIR21. We obtained CCA biopsies from patients, cultured them as organoids (patient-derived organo

SUBMITTER: Lampis A 

PROVIDER: S-EPMC5863695 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature