title: MiR-30c-2* negative regulated MTA-1 expression involved in metastasis and drug resistance of HPV-infected non-small cell lung cancer.
abstract: MiR-30c-2* is considered to be a tumor suppressor microRNA in various cancers and is associated with gemcitabine sensitivity of lung cancer cells. Downregulation of miR-30c-2* promotes tumor invasion via increased expression of metastasis-associated protein-1. We hypothesized that downregulated expression of miR-30c-2* was involved in human papillomavirus-associated lung tumorigenesis and drug resistance.
  
  
  
  We examined whether expression of human papillomavirus 16/18 oncoprotein and miR-30c-2*-associated genes could be linked to patient outcome by collecting 319 lung tumors from patients with non-small cell lung cancer to determine expression of human papillomavirus 16/18 E6 protein, miR-30c-2*, and miR-30c-2* downstream metastasis-associated protein-1 mRNA by immunohistochemical and real-time polymerase chain reaction analysis.
  
  
  
  Our results showed that miR-30C-2* levels were increased 45-fold in the E6-knockdown TL-1 cells when compared with levels in the parental cells. More interestingly, metastasis-associated protein-1 expression correlated negatively with miR-30C-2* and positively with human papillomavirus 16 E6 protein expression in lung tumors from lung cancer patients. Metastasis-associated protein-1 expression levels in the tumor tissues correlated positively with tumor stage and nodal metastasis. Patients with high metastasis-associated protein-1 expression, and especially patients infected with human papillomavirus, experienced a poor clinical outcome, tumor recurrence, and a poor therapeutic response compared with those with low metastasis-associated protein-1 expression.
  
  
  
  These results showed that miR-30C-2* and levels of downstream metastasis-associated protein-1 gene expression in the tumor tissues of patients could be useful in predicting clinical outcome and therapeutic response and in selecting useful therapeutic drugs for lung cancer patients, especially patients with human papillomavirus infection.
authors: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; School of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors: Yi-Liang
authors: YL
authors: Wu
authors: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; Cancer Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan; Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan; Division of Thoracic Surgery, Ningbo Medical Center Lihuili Eastern Hospital, Ningbo, China.
authors: Nan-Yung
authors: NY
authors: Hsu
authors: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors: Frank
authors: F
authors: Cheau-Feng Lin
authors: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; Cancer Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
authors: Huei
authors: H
authors: Lee
authors: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; Cancer Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address: ywc@tmu.edu.tw.
authors: Ya-Wen
authors: YW
authors: Cheng
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators
chemical_list: D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; C089320:MTA1 protein, human; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012097:Repressor Proteins; D015534:Trans-Activators; D006655:Histone Deacetylases