miR‐18a activates Wnt pathway in ER‐positive breast cancer and is associated with poor prognosis
| Autor: | Srinath B S, Aruna Korlimarla, Hari P S, Sridhar T S, Roma Kaul, Annie Alexander, Rohini Raghavan, Madhumathy G. Nair, Jyothi S. Prabhu, Savitha Rajarajan |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Wnt pathway Estrogen receptor Breast Neoplasms miR‐18a Biology migration lcsh:RC254-282 03 medical and health sciences Basal (phylogenetics) Cytokeratin 0302 clinical medicine Breast cancer medicine Humans Radiology Nuclear Medicine and imaging Epigenetics Planar cell polarity pathway Wnt Signaling Pathway Original Research Cancer Biology Wnt signaling pathway Middle Aged lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Prognosis Survival Analysis MicroRNAs 030104 developmental biology Oncology Receptors Estrogen 030220 oncology & carcinogenesis Cancer research Female Estrogen receptor alpha Hormone ER‐positive breast cancer |
| Zdroj: | Cancer Medicine Cancer Medicine, Vol 9, Iss 15, Pp 5587-5597 (2020) |
| ISSN: | 2045-7634 |
| Popis: | Despite the established benefits of long‐term endocrine therapy, women with hormone receptor‐positive breast cancer remain at risk for late relapse. The basis of this is multi‐factorial including genetic, epigenetic, and host factors. In this study we have explored the epigenetic regulation of estrogen receptor (ER)‐dependent molecular and cellular phenotype by hsa‐miR‐18a‐5p using well‐established human ER‐positive (ER+) breast cancer cell lines. miR‐18a was overexpressed in MCF7 and ZR‐75‐1 and this led to an increase in the proliferative ability of the cells and concurrently resulted in decreased expression of luminal markers and higher expression of the basal marker, cytokeratin 14. The cells became more migratory with a significant repression of E‐cadherin and activation of the Wnt noncanonical pathway. We observed an activation of the planar cell polarity (PCP) pathway with increased activation of JNK pathway and eventually change in actin dynamics. There was increased F‐actin polymerization in cells with higher expression of miR‐18a. Examination of miR‐18a expression in a set of human ER+ breast cancer specimens showed a negative correlation between miR‐18a and ESR1 transcripts as well as ER protein. Kaplan‐Meier survival analysis of the cohort stratified by tumor hsa‐miR‐18a‐5p levels produced significant differences in disease‐free survival (log rank P Through the manuscript, we have tried to explore the epigenetic regulation of estrogen receptor (ER) dependent molecular and cellular phenotype by hsa‐miR‐18a‐5p. High levels of miR‐18a activates the epigenetic pathway of repression of the luminal phenotype through activation of Wnt pathway. |
| Databáze: | OpenAIRE |
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