MicroRNA-143 is associated with pathological complete response and regulates multiple signaling proteins in breast cancer

Raúl García-Vázquez, Laurence A. Marchat, Erika Ruíz-García, Horacio Astudillo-De la Vega, Abelardo Meneses-García, Claudia Arce-Salinas, Enrique Bargallo-Rocha, Ángeles Carlos-Reyes, José Sullivan López-González, Carlos Pérez-Plasencia, Rosalío Ramos-Payán, Maribel Aguilar-Medina, César López-Camarillo

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11 Scopus citations

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.

Original languageEnglish
JournalTechnology in Cancer Research and Treatment
Volume18
DOIs
StatePublished - 2019

Keywords

  • Breast cancer
  • Cell migration
  • Cell proliferation
  • MiR-143
  • Neoadjuvant therapy
  • Pathological complete response
  • Signaling pathways

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