title: p21WAF1/CIP1 gene transcriptional activation exerts cell growth inhibition and enhances chemosensitivity to cisplatin in lung carcinoma cell.
abstract: BACKGROUND
  Non-small-cell lung carcinomas (NSCLCs) exhibit poor prognosis and are usually resistant to conventional chemotherapy. Absence of p21WAF1/CIP1, a cyclin-dependent kinase (cdk) inhibitor, has been linked to drug resistance in many in vitro cellular models. RNA activation (RNAa) is a transcriptional activation phenomena guided by double-strand RNA (dsRNA) targeting promoter region of target gene.
  
  
  METHODS
  In this study, we explored the effect of up-regulation of p21 gene expression on drug-resistance in A549 non-small-cell lung carcinoma cells by transfecting the dsRNA targeting the promoter region of p21 into A549 cells.
  
  
  RESULTS
  Enhanced p21 expression was observed in A549 cells after transfection of dsRNA, which was correlated with a significant growth inhibition and enhancement of chemosensitivity to cisplatin in A549 cells in vitro. Moreover, in vivo experiment showed that saRNA targeting the promoter region of p21 could significantly inhibit A549 xenograft tumor growth.
  
  
  CONCLUSIONS
  These results indicate that p21 plays a role in lung cancer drug-resistance process. In addition, this study also provides evidence for the usage of saRNA as a therapeutic option for up-regulating lower-expression genes in lung cancer.
authors.affiliation: Department of Clinical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Wei
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhao
authors.forename: Min
authors.initials: M
authors.lastname: Long
authors.forename: Yuan
authors.initials: Y
authors.lastname: Han
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Lin
authors.forename: Jihong
authors.initials: J
authors.lastname: Ren
authors.forename: Ting
authors.initials: T
authors.lastname: He
authors.forename: Huizhong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002277:Carcinoma / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D009368:Neoplasm Transplantation; D011401:Promoter Regions, Genetic; D012313:RNA / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012330:RNA, Double-Stranded; D012313:RNA; D002945:Cisplatin