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MicroRNA-143 is Associated With Pathological Complete Response and Regulates Multiple Signaling Proteins in Breast Cancer.
- Source :
-
Technology in cancer research & treatment [Technol Cancer Res Treat] 2019 Jan 01; Vol. 18, pp. 1533033819827309. - Publication Year :
- 2019
-
Abstract
- Almost 55% to 80% of patients with breast cancer have an unfavorable pathological complete response to chemotherapy. MicroRNAs are small noncoding RNAs involved in cancer progression; however, their utility as predictors of pathological complete response to neoadjuvant chemotherapy is unclear. Here, we investigated if miR-143 could discriminate between pathological complete response and no-polymerase chain reaction of patients with locally advanced triple negative breast cancer that have received a fluorouracil-cisplatin/paclitaxel-based neoadjuvant treatment. Data showed that miR-143 exhibited a significant low expression ( P < .0006) in patients that achieved pathological complete response in comparison to nonresponder group. Receiver operating characteristic curve analysis suggested that miR-143 could be a good predictor of pathological complete response (area under curve = 0.849, P < .0006). Moreover, Kaplan-Meier analysis indicated that before neoadjuvant therapy low levels of miR-143 were associated to increased disease free survival. To gain insights into cellular functions of miR-143, we firstly showed that miR-143 was severely repressed in breast cancer cell lines and tumors in comparison to normal mammary cells and tissues. Ectopic restoration of miR-143 using RNA mimics inhibited both cell proliferation and migration and sensitized breast cancer cells to cisplatin therapy in vitro. To decipher the signaling networks regulated by miR-143, we used a high-throughput enzyme-linked immunosorbent assay-based phosphorylation antibody array. Phospho-proteomic profiling revealed that miR-143 coordinately reduced the protein levels and phosphorylation status of multiple oncoproteins involved in AKT, WNT/β-catenin, SAPK/JNK, FAK, and JAK/STAT signaling pathways. Moreover, low miR-143 and high GSK3-β, RAF1, paxillin, and p21CIP1 expression levels in a large cohort of patients with breast cancer were associated with worst outcome. In summary, miR-143 could be a potential predictor of response to neoadjuvant therapy and it may function as a divergent regulator of diverse signaling networks to suppress cell proliferation and migration in breast cancer.
- Subjects :
- Biomarkers, Tumor genetics
Breast Neoplasms drug therapy
Breast Neoplasms genetics
Breast Neoplasms metabolism
Cell Movement
Cell Proliferation
Drug Resistance, Neoplasm
Female
Gene Expression Profiling
Humans
Signal Transduction
Tumor Cells, Cultured
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Biomarkers, Tumor metabolism
Breast Neoplasms pathology
Gene Expression Regulation, Neoplastic
MicroRNAs genetics
Neoadjuvant Therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1533-0338
- Volume :
- 18
- Database :
- MEDLINE
- Journal :
- Technology in cancer research & treatment
- Publication Type :
- Academic Journal
- Accession number :
- 30755102
- Full Text :
- https://doi.org/10.1177/1533033819827309