L-Y Sha1, Y Zhang, W Wang, X Sui, S-K Liu, T Wang, H Zhang. 1. Department of Pharmacy, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China. Huizhange@outlook.com.
Abstract
OBJECTIVE: MiR-18a is a miRNA that is aberrantly overexpressed in triple-negative breast cancer (TNBC). However, its biophysical function in TNBC is still not clear. In this study, we investigated the association among miR-18a dysregulation, Dicer dysregulation and paclitaxel (PTX) resistance in TNBC cells. PATIENTS AND METHODS: 20 TNBC patients who received neoadjuvant chemotherapy before surgery were recruited. MiR-18a expression was quantified using QRT-PCR. The effects of miR-18a overexpression or knockdown on cell viability and apoptosis of PTX sensitive MDA-MB-231 cells and PTX resistant MDA-MB-231 cells after PTX treatment were studied. The influence of miR-18a overexpression on Dicer expression was measured by qRT-PCR and Western blot analysis. RESULTS: Tissues from patients with stable disease (SD, n = 5) and progressive disease (PD, n = 2) to paclitaxel (PTX) containing neoadjuvant chemotherapy had significantly higher miR-18a expression than that from patients with partial response (PR, n = 13). MDA-MB-231/PTX cells had higher miR-18a expression than MDA-MB-231 cells. MiR-18a overexpression directly led to Dicer repression at mRNA and protein level. MiR-18a overexpression significantly increased PTX IC50 and reduced PTX induced cell apoptosis, while miR-18a suppression substantially decreased PTX IC50 and increased PTX induced cell apoptosis. CONCLUSIONS: This study found that miR-18a is an important miRNA that suppresses Dicer expression and increases PTX resistance in TNBC cells.
OBJECTIVE:MiR-18a is a miRNA that is aberrantly overexpressed in triple-negative breast cancer (TNBC). However, its biophysical function in TNBC is still not clear. In this study, we investigated the association among miR-18a dysregulation, Dicer dysregulation and paclitaxel (PTX) resistance in TNBC cells. PATIENTS AND METHODS: 20 TNBC patients who received neoadjuvant chemotherapy before surgery were recruited. MiR-18a expression was quantified using QRT-PCR. The effects of miR-18a overexpression or knockdown on cell viability and apoptosis of PTX sensitive MDA-MB-231 cells and PTX resistant MDA-MB-231 cells after PTX treatment were studied. The influence of miR-18a overexpression on Dicer expression was measured by qRT-PCR and Western blot analysis. RESULTS: Tissues from patients with stable disease (SD, n = 5) and progressive disease (PD, n = 2) to paclitaxel (PTX) containing neoadjuvant chemotherapy had significantly higher miR-18a expression than that from patients with partial response (PR, n = 13). MDA-MB-231/PTX cells had higher miR-18a expression than MDA-MB-231 cells. MiR-18a overexpression directly led to Dicer repression at mRNA and protein level. MiR-18a overexpression significantly increased PTX IC50 and reduced PTX induced cell apoptosis, while miR-18a suppression substantially decreased PTX IC50 and increased PTX induced cell apoptosis. CONCLUSIONS: This study found that miR-18a is an important miRNA that suppresses Dicer expression and increases PTX resistance in TNBC cells.
Authors: Penn Muluhngwi; Abirami Krishna; Stephany L Vittitow; Joshua T Napier; Kirsten M Richardson; Mackenzie Ellis; Justin L Mott; Carolyn M Klinge Journal: Cancer Lett Date: 2016-12-13 Impact factor: 8.679
Authors: Alma D Campos-Parra; Gerardo Cuamani Mitznahuatl; Abraham Pedroza-Torres; Rafael Vázquez Romo; Fany Iris Porras Reyes; Eduardo López-Urrutia; Carlos Pérez-Plasencia Journal: Int J Mol Sci Date: 2017-06-02 Impact factor: 5.923