title: Downregulation of miR-221 enhances the sensitivity of human oral squamous cell carcinoma cells to Adriamycin through upregulation of TIMP3 expression.
abstract: Aberrantly expressed microRNAs (miRNAs) are involved in oral tumorigenesis since they can alter the expression of proteins involved in cancer progression. It remains unclear whether miRNA-221 influences the resistance of human oral squamous cell carcinoma cells to Adriamycin. We therefore investigated the role of miR-221 in the sensitivity of oral squamous cell carcinoma cells to chemotherapy. Tca8113 and UM2 cells were treated with different concentrations of Adriamycin. Quantitative real-time PCR (qRT-PCR) revealed miR-221 upregulation after Adriamycin treatment of Tca8113 and UM2 cells. By using miR-221 inhibitor mimics, we found that depleting cells of miR-221 increases the sensitivity of the cells to Adriamycin. The expression of tissue inhibitor of metalloproteinase-3 (TIMP3), a target of miR-221, was decreased in cells treated with Adriamycin. TIMP3 depletion reversed the effect of a miR-221 inhibitor mimics on cell survival rates and apoptosis. Together, these results reveal that silencing of miR-221 enhances the sensitivity of human oral squamous cell carcinoma cells to Adriamycin through upregulation of TIMP3 expression.
authors.affiliation: Department of Oral & Maxillofacial Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Oral & Maxillofacial Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Wangxiang
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Oral & Maxillofacial Surgery, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou 510055, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Stomatology, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510655, China.
authors.forename: Zhaoqiang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of oral and maxillofacial surgery of Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Oral & Maxillofacial Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Oral & Maxillofacial Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Xueqiang
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Oral & Maxillofacial Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Anxun
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Oral & Maxillofacial Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China. Electronic address: zhoychen@tom.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D002470:Cell Survival; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009062:Mouth Neoplasms / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D035683:MicroRNAs; D019717:Tissue Inhibitor of Metalloproteinase-3; C525709:MIR221, human; C088390:TIMP3 protein, human
keywords: Adriamycin; Oral squamous cell carcinoma; TIMP3; miR-221