title: miR-27a regulates the sensitivity of breast cancer cells to cisplatin treatment via BAK-SMAC/DIABLO-XIAP axis.
abstract: MicroRNA-27a (miR-27a) has been reported to be an onco-microRNA in multiple cancers promoting tumor growth and metastasis, but the role of miR-27a in regulating the cancer sensitivity to chemotherapy remains unknown. In this study, upregulation of miR-27a was validated by real-time PCR analysis in breast cancer (BC) cell lines and samples of BC patients. A negative correlation between miR-27a and bak was also observed in normal breast epithelial cell line MCF-10A and BC cell lines, suggesting that the bak is the potential target of miR-27a. miR-27a could modulate the growth and metastasis of BC cells. More importantly, we found that knockdown of miR-27a by the specific inhibitors significantly increased the sensitivity of T-47D cells to cisplatin (CDDP) treatment. After further investigation, we indicated that the knockdown of miR-27a promoted the apoptosis via mitochondrial pathway in T-47D cells treated with CDDP, depending on the BAK-second mitochondria-derived activator of caspase/direct IAP binding protein with low pI (SMAC/DIABLO)-X-linked inhibitor of apoptosis (XIAP) axis. Interestingly, we found that the sensitivity of T-47D cells to some other chemotherapeutic agents (5-fluorouracil, doxorubicin, and tumor necrosis factor-related apoptosis-inducing ligand) was also regulated by miR-27a. These findings improve our understanding of the role of miR-27a in breast cancer and might provide a novel strategy for cancer therapy.
authors.affiliation: Surgical Oncology Department, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Town, Ouhai District, Wenzhou City, Zhejiang Province, 325000, China.
authors.forename: Sumei
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Surgical Oncology Department, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Town, Ouhai District, Wenzhou City, Zhejiang Province, 325000, China.
authors.forename: Qidi
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Surgical Oncology Department, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Town, Ouhai District, Wenzhou City, Zhejiang Province, 325000, China.
authors.forename: Shurong
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Surgical Oncology Department, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Town, Ouhai District, Wenzhou City, Zhejiang Province, 325000, China.
authors.forename: Kuailu
authors.initials: K
authors.lastname: Lin
authors.affiliation: Surgical Oncology Department, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Town, Ouhai District, Wenzhou City, Zhejiang Province, 325000, China.
authors.forename: Jie
authors.initials: J
authors.lastname: You
authors.affiliation: Surgical Oncology Department, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Town, Ouhai District, Wenzhou City, Zhejiang Province, 325000, China. zjzxh1974@126.com.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics* / Q000378:metabolism; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D024101:Mitochondrial Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; D050998:bcl-2 Homologous Antagonist-Killer Protein; D002945:Cisplatin
keywords: BAK; Breast cancer; Cisplatin; SMAC/DIABLO; XIAP; miR-27a