Circular RNA circ-ERBB2 Elevates the Warburg Effect and Facilitates Triple-Negative Breast Cancer Growth by the MicroRNA 136-5p/Pyruvate Dehydrogenase Kinase 4 Axis
- 1 October 2021
- journal article
- research article
- Published by Taylor & Francis Ltd in Molecular and Cellular Biology
- Vol. 41 (10), e0060920
- https://doi.org/10.1128/mcb.00609-20
Abstract
Triple negative breast cancer (TNBC) is an aggressive histological subtype of breast cancer. It has been reported that that circRNA circ-ERBB2 (circBase ID: hsa_circ_0007766) is mainly distributed in the cytoplasm of TNBC cells and promotes the proliferation and invasion of TNBC cells. This study aimed to explore the molecular mechanism of circ-ERBB2 regulating the progression of TNBC. Expression of circ-ERBB2 was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Loss-of-function experiments were performed to investigate the function of circ-ERBB2 in TNBC cells in vitro and in vivo. The regulatory mechanism of circ-ERBB2 was surveyed by bioinformatics analysis, dual-luciferase reporter and RNA immunoprecipitation (RIP) or RNA pull-down assays. We observed that Circ-ERBB2 was overexpressed in TNBC, and TNBC patients with high circ-ERBB2 expression had a poor prognosis. Functionally, circ-ERBB2 knockdown constrained TNBC growth in vivo and reduced Warburg effect, accelerated apoptosis, repressed proliferation, migration, and invasion of TNBC cell in vitro. Mechanically, circ-ERBB2 sponged miR-136-5p to elevate pyruvate dehydrogenase kinase 4 (PDK4) expression. In conclusion, circ-ERBB2 facilitated Warburg effect and malignancy of TNBC cells by the miR-136-5p/PDK4 pathway, at least in part. This study supported circ-ERBB2 as a prognostic indicator for TNBC.Keywords
Funding Information
- CHENGDU MUNICIPAL HEALTH COMMISSION PROJECT (2019107)
This publication has 39 references indexed in Scilit:
- Targeting the Warburg effect for cancer treatment: Ketogenic diets for management of gliomaSeminars in Cancer Biology, 2017
- Loss of the novel mitochondrial protein FAM210B promotes metastasis via PDK4-dependent metabolic reprogrammingCell Death & Disease, 2017
- Triple-negative breast cancer: challenges and opportunities of a heterogeneous diseaseNature Reviews Clinical Oncology, 2016
- The Warburg Effect: How Does it Benefit Cancer Cells?Trends in Biochemical Sciences, 2016
- Circular RNA: A new star of noncoding RNAsCancer Letters, 2015
- Pyruvate Dehydrogenase Kinases: Therapeutic Targets for Diabetes and CancersDiabetes & Metabolism Journal, 2015
- Breast-Conserving Therapy for Triple-Negative Breast CancerJAMA Surgery, 2014
- New Strategies for Triple-Negative Breast Cancer—Deciphering the HeterogeneityClinical Cancer Research, 2014
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Warburg effect mechanism as the target for theoretical substantiation of new possibility cancer disease treatmentCritical Reviews™ in Eukaryotic Gene Expression, 2011