Unknown

Dataset Information

0

A novel miR-34a target, protein kinase D1, stimulates cancer stemness and drug resistance through GSK3/β-catenin signaling in breast cancer.


ABSTRACT: One of the properties of human breast cancer cells is cancer stemness, which is characterized by self-renewal capability and drug resistance. Protein kinase D1 (PRKD1) functions as a key regulator of many cellular processes and is downregulated in invasive breast cancer cells. In this study, we found that PRKD1 was upregulated in MCF-7-ADR human breast cancer cells characterized by drug resistance. Additionally, we discovered that PRKD1 expression was negatively regulated by miR-34a binding to the PRKD1 3'-UTR. PRKD1 expression increased following performance of a tumorsphere formation assay in MCF-7-ADR cells. We also found that reduction of PRKD1 by ectopic miR-34a expression or PRKD1 siRNA treatment resulted in suppressed self-renewal ability in breast cancer stem cells. Furthermore, we confirmed that the PRKD1 inhibitor CRT0066101 reduced phosphorylated PKD/PKCμ, leading to suppression of breast cancer stemness through GSK3/β-catenin signaling. PRKD1 inhibition also influenced apoptosis initiation in MCF-7-ADR cells. Tumors from nude mice treated with miR-34a or CRT0066101 showed suppressed tumor growth, proliferation, and induced apoptosis. These results provide evidence that regulation of PRKD1, a novel miR-34a target, contributes to overcoming cancer stemness and drug resistance in human breast cancer.

SUBMITTER: Kim do Y 

PROVIDER: S-EPMC4924752 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

A novel miR-34a target, protein kinase D1, stimulates cancer stemness and drug resistance through GSK3/β-catenin signaling in breast cancer.

Kim Do Yeon do Y   Park Eun Young EY   Chang EunSun E   Kang Hyeok-Gu HG   Koo Yoonjin Y   Lee Eun Ji EJ   Ko Je Yeong JY   Kong Hyun Kyung HK   Chun Kyung-Hee KH   Park Jong Hoon JH  

Oncotarget 20160301 12


One of the properties of human breast cancer cells is cancer stemness, which is characterized by self-renewal capability and drug resistance. Protein kinase D1 (PRKD1) functions as a key regulator of many cellular processes and is downregulated in invasive breast cancer cells. In this study, we found that PRKD1 was upregulated in MCF-7-ADR human breast cancer cells characterized by drug resistance. Additionally, we discovered that PRKD1 expression was negatively regulated by miR-34a binding to t  ...[more]

Similar Datasets

| S-EPMC7142390 | biostudies-literature
| S-EPMC4040665 | biostudies-literature
| S-EPMC3381742 | biostudies-literature
| S-EPMC8910270 | biostudies-literature
| S-EPMC4990398 | biostudies-literature
| S-EPMC5829510 | biostudies-literature
| S-EPMC7378835 | biostudies-literature
| S-EPMC2562938 | biostudies-literature
| S-EPMC6609830 | biostudies-literature
| S-EPMC3327669 | biostudies-other