Affiliation:
1. The Central Hospital of Wuhan
2. Wuhan University of Science and Technology
3. Baylor College of Medicine
Abstract
Abstract
Background
Metastasis and drug resistance of breast cancer have become a barrier to treating patients successfully. Long noncoding RNAs (lncRNAs) are known as vital players in cancer development and progression.
Methods
The RT-qPCR were used to detect the gene expression. Colony formation assay, would healing assay, and transwell assay were performed to investigate oncogenic functions of cells. CCK8 assay was used to detect the cell vability. Western blot was applied to detect the protein level. Dual-luciferase reporter assay was used to determine the relationship between molecules. Mouse orthotopic xenograft tumor models were established to evaluate the effects of BCAR4 on tumor growth and metastasis in vivo.
Results
LncRNA BCAR4 was significantly increased in breast cancer patients’ tissues and plasma and upregulated in breast cancer cell lines. BCAR4 upregulation was correlated with the TNM stages and decreased after surgical removal of breast tumors. Silencing of BCAR4 suppressed breast cancer cell colony formation, migration, invasion, and xenograft tumor growth and promoted chemo-sensitivity. Mechanistically, BCAR4 facilitates breast cancer migration and invasion via the miR-644a-CCR7 axis of the MAPK pathway. BCAR4 promotes ABCB1 expression indirectly by binding to and down-regulating miR-644a to induce chemo-resistance in breast cancer.
Conclusions
Our findings provide insights into the oncogenic role of BCAR4 and implicate BCAR4 as a potential diagnostic biomarker and a promising therapeutic agent to suppress metastasis and inhibit chemo-resistance of breast cancer.
Publisher
Research Square Platform LLC
Reference37 articles.
1. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries;Sung H;Cancer J Clin,2021
2. Local Recurrence and Breast Oncological Surgery in Young Women With Breast Cancer: The POSH Observational Cohort Study;Maishman T;Ann Surg,2017
3. Breast cancer: molecular mechanisms of underlying resistance and therapeutic approaches;Tufail M;Am J Cancer Res,2022
4. Reversing Multidrug Resistance by Multiplexed Gene Silencing for Enhanced Breast Cancer Chemotherapy;Li Y;ACS Appl Mater Interfaces,2018
5. The Mechanisms of lncRNA-Mediated Multidrug Resistance and the Clinical Application Prospects of lncRNAs in Breast Cancer;Ye P;Cancers (Basel),2022