scholarly journals miR-193b Modulates Resistance to Doxorubicin in Human Breast Cancer Cells by Downregulating MCL-1

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Jingpei Long ◽  
Zhiwei Ji ◽  
Kai Jiang ◽  
Zhaoyang Wang ◽  
Guanmin Meng

MicroRNAs (miRNAs) family, which is involved in cancer development, proliferation, apoptosis, and drug resistance, is a group of noncoding RNAs that modulate the expression of oncogenes and antioncogenes. Doxorubicin is an active cytotoxic agent for breast cancer treatment, but the acquisition of doxorubicin resistance is a common and critical limitation to cancer therapy. The aim of this study was to investigate whether miR-193b mediated the resistance of breast cancer cells to doxorubicin by targeting myeloid cell leukemia-1 (MCL-1). In this study, we found that miR-193b levels were significantly lower in doxorubicin-resistant MCF-7 (MCF-7/DOXR) cells than in the parental MCF-7 cells. We observed that exogenous miR-193b significantly suppressed the ability of MCF-7/DOXR cells to resist doxorubicin. It demonstrated that miR-193b directly targeted MCL-1 3′-UTR (3′-Untranslated Regions). Further studies indicated that miR-193b sensitized MCF-7/DOXR cells to doxorubicin through a mechanism involving the downregulation of MCL-1. Together, our findings provide evidence that the modulation of miR-193b may represent a novel therapeutic target for the treatment of breast cancer.

2013 ◽  
Vol 43 (5) ◽  
pp. 1481-1486 ◽  
Author(s):  
VASYL F. CHEKHUN ◽  
NATALIA Yu. LUKYANOVA ◽  
ANATOLIY P. BURLAKA ◽  
NATALIA A. BEZDENEZHNYKH ◽  
SVITLANA I. SHPYLEVA ◽  
...  

2003 ◽  
Vol 17 (10) ◽  
pp. 2002-2012 ◽  
Author(s):  
Olga A. Sukocheva ◽  
Lijun Wang ◽  
Nathaniel Albanese ◽  
Stuart M. Pitson ◽  
Mathew A. Vadas ◽  
...  

Abstract Current understanding of cytoplasmic signaling pathways that mediate estrogen action in human breast cancer is incomplete. Here we report that treatment with 17β-estradiol (E2) activates a novel signaling pathway via activation of sphingosine kinase (SphK) in MCF-7 breast cancer cells. We found that E2 has dual actions to stimulate SphK activity, i.e. a rapid and transient activation mediated by putative membrane G protein-coupled estrogen receptors (ER) and a delayed but prolonged activation relying on the transcriptional activity of ER. The E2-induced SphK activity consequently activates downstream signal cascades including intracellular Ca2+ mobilization and Erk1/2 activation. Enforced expression of human SphK type 1 gene in MCF-7 cells resulted in increases in SphK activity and cell growth. Moreover, the E2-dependent mitogenesis were highly promoted by SphK overexpression as determined by colony growth in soft agar and solid focus formation. In contrast, expression of SphKG82D, a dominant-negative mutant SphK, profoundly inhibited the E2-mediated Ca2+ mobilization, Erk1/2 activity and neoplastic cell growth. Thus, our data suggest that SphK activation is an important cytoplasmic signaling to transduce estrogen-dependent mitogenic and carcinogenic action in human breast cancer cells.


1993 ◽  
Vol 215 (3) ◽  
pp. 671-676 ◽  
Author(s):  
Noriyoshi KIDA ◽  
Tomoaki YOSHIMURA ◽  
Haruo TAKAHASHI ◽  
Seiji NAGAO ◽  
Yoshinori NOZAWA ◽  
...  

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