title: MiR-222 targeted PUMA to improve sensitization of UM1 cells to cisplatin.
abstract: microRNAs have been shown to play critical roles in regulating the chemosensitivity of cancer cells. As a member of the oncogenic miRNAs (oncomiRs), miR-222 has been reported to drive the oncogenesis of many types of malignancies. However, little is known concerning the specific role of miR-222 in human oral squamous cell carcinoma (OSCC). The present study explored the role and mechanism of miR-222 in increasing the expression of p53 up-regulated modulator of apoptosis (PUMA) and enhancing the sensitivity of OSCC to cisplatin (CDDP). Results showed that antisense (As)-miR-222 inhibits the expression of miR-222. In contrast, PUMA was dramaticallyup-regulated. IC50 values were significantly decreased in cells treated with As-miR-222 combined with CDDP, to a greater extent than in cells treated with CDDP alone. Furthermore, As-miR-222 enhanced apoptosis and inhibited the invasiveness of UM1 cells. Analysis of the above data suggested that, in UM1 cells, there might be a regulatory loop between miR-222 and PUMA, and that miR-222 inhibition increased the chemosensitivity to CDDP. These findings demonstrated that down-regulation of miR-222 could enhance the chemosensitivity of human OSCC cells to CDDP, and that the combination of As-miR-222 and CDDP could be an effective therapeutic strategy by boosting the expression of PUMA for controlling the growth of OSCC.
authors.affiliation: Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055, China. jiangfangfang0628@163.com.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055, China. zhaowei3@mail.sysu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055, China. zhoulj7@mail2.sysu.edu.cn.
authors.forename: Lijie
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055, China. sumsliu@hotmail.com.
authors.forename: Zifeng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055, China. wendysums@hotmail.com.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Li
authors.affiliation: Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055, China. yudsh@mail.sysu.edu.cn.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Yu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D009361:Neoplasm Invasiveness; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016372:RNA, Antisense / Q000378:metabolism; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; D002945:Cisplatin; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D016372:RNA, Antisense; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; C438378:BBC3 protein, human; C525710:MIR222, human