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Title:
Olaparib Upregulates miR-630 Expression to Enhance the Chemotherapeutic Sensitivity of BRCA-1 Mutant Triple-Negative Breast Cancer Cell Lines
Authors:  Qun Hu, Ph.D., M.D., Chao Li, M.M., Caixia Liu, M.M., Lijuan Chang, M.M., Ze Xing, M.M., Haiyan Zhao, M.D., Ranhua Cao, M.D., and Wuyun Su, M.M.
  Objective: To explore the role of BRCA-1 in path- ogenesis of triple-negative breast cancer (TNBC) and molecular mechanism.
Study Design:
Two BRCA-1 mutant TNBC cell lines, MDA-MB-436 and HCC1937, were screened for differentially expressed miRNAs by miRNA microarray after treatment by carboplatin plus gemcitabine with or without the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib. After verification by qRT-PCR, miR-630 was selected for further studies. After treatment or transfection, cell growth was detected by MTT assay, and cell migration and invasion capacities were tested by scratch and transwell assays, respectively.
Results:
In BRCA-1 mutant MDA-MB-436 and HCC1937 cells, carboplatin plus gemcitabine combined with PARP inhibitor olaparib upregulated miR-630 expression. Overexpression of miR-630 suppressed cell proliferation, migration, and invasion, whereas inhibition of miR-630 had opposite effects.
Conclusion:
As a tumor suppressor, miR-630 plays an important role in increasing the chemotherapeutic sensitivity of PARP inhibitors. This may be one of the mechanisms by which PARP inhibitors enhance the sensitivity of BRCA-1 mutant TNBC cells to chemotherapy.
Keywords:  breast cancer; carboplatin; chemother­ apy; immunotherapy; miR­630; olaparib; triple­ negative breast cancer
   
   
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