en زیست شناسی مولکولی Molecular biology پژوهشي Research <div style="text-align: justify;"><span style="font-size:11pt"><span style="line-height:normal"><span style="text-autospace:none"><span calibri="" style="font-family:"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black">Background: </span></span></span></b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black">Down-regulation of <i>miRNA-15a </i>and <i>miRNA-16-1 </i>is associated with Bcl-2 and Mcl-1 expression and chemoresistance in tumor cells. In this study, the combined effect of <i>miRNA-15a</i> and <i>miRNA-16-1 </i>on apoptosis and sensitivity of the chronic lymphocytic leukemia (CLL) cells to fludarabine and ABT-199 was investigated.</span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="text-autospace:none"><span calibri="" style="font-family:"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black"></span></span></span></b></span></span></span></span><span style="font-size:11pt"><span style="line-height:normal"><span style="text-autospace:none"><span calibri="" style="font-family:"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black">Materials and Methods: </span></span></span></b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black">The experiment groups were as follows: ABT-199, negative control (NC) miRNA, <i>miRNA-15a</i>, miRNA-16, <i>miRNA-15a</i>+<i>miRNA-16</i>, NC miRNA+ABT-199, <i>miRNA-15a</i>+<i>miRNA-16</i>+ABT-199, erlotinib blank control, miRNA blank control and combination blank control. The expression levels of <i>Bcl-2 </i>and <i>Mcl-1 </i>were measured using quantitative real-time PCR</span></span></span></span></span></span></span><span style="font-size:11pt"><span style="line-height:normal"><span style="text-autospace:none"><span calibri="" style="font-family:"><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black"> (qRT-PCR). The effect of treatments on cell growth and survival was measured by trypan blue staining and MTT (3-[4, 5 dimethylthiazol-2-yl]-2, 5 diphenyltetrazolium bromide) assay, respectively. Apoptosis was measured using caspase-3 activity and ELISA cell death assays.</span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="text-autospace:none"><span calibri="" style="font-family:"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black">Results: </span></span></span></b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black">Transfection of <i>miRNA-15a </i>or <i>miRNA-16-1 </i>significantly suppressed the expression of <i>Bcl-2 </i>and <i>Mcl-1 </i>in a time-dependent manner (P<0.05 versus negative control miRNA or blank control).<i> </i>Other experiments showed that up-regulation of <i>miRNA-15a </i>or <i>miRNA-16-1 </i>decreased cell growth,<i> </i>induced apoptosis, and synergistically lowered the IC50 value of fludarabine and ABT-199 in CLL<i> </i>cells. Moreover, co-transfection of two miRNAs showed a more significant effect on cell survival,<i> </i>apoptosis, and drug sensitivity than single transfection.<i></i></span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="text-autospace:none"><span calibri="" style="font-family:"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black">Conclusion: </span></span></span></b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black">Our study shows that <i>miRNA-15a </i>and <i>miRNA-16-1 </i>can effectively enhance the anticancer effects of fludarabine and ABT-199 in CLL cells and may offer a new promising therapeutic strategy for CLL-resistant patients.</span></span></span></span></span></span></span></div> ABT-199, fludarabine, Mcl-1, miRNA-15a, miRNA-16-1 235 248 http://rmm.mazums.ac.ir/browse.php?a_code=A-10-750-2&slc_lang=en&sid=1 Nooshin Ashofteh n_ashofteh@yahoo.com 100319475328460013130 100319475328460013130 No Students Research Committee, Arak University of Medical Sciences, Arak, Iran Razieh Amini raziehamini1990@gmail.com 100319475328460013131 100319475328460013131 No Department of Molecular Medicine and Biotechnology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran Alireza Amani dramani.ortho@yahoo.com 100319475328460013132 100319475328460013132 No Department of Orthopedic, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran Hadi karami hadimolmed@gmail.com 100319475328460013133 100319475328460013133 Yes Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak, Iran