title: Silencing of the hPOT1 gene by RNA inference promotes apoptosis and inhibits proliferation and aggressive phenotype of gastric cancer cells, likely through up-regulating PinX1 expression.
abstract: BACKGROUND
  The human protection of telomeres 1 (hPOT1) protein, a single-strand telomeric DNA binding protein, plays an important role in telomere protection and telomere length regulation. However, its effect on invasion of gastric cancer remains unclear.
  
  
  OBJECTIVE
  To explore the role of hPOT1 in the proliferation and invasion of gastric cancer cells.
  
  
  METHODS
  The gastric expression of hPOT1 was examined in normal gastric mucosa (n=25), intestinal metaplasia (n=20), gastric dysplasia (n=20) and gastric cancer (n=150) by immunohistochemistry. The mean optical density (MOD) of the immunostaining was determined by semi-quantitative image analysis. The role of hPOT1 in the cell proliferation, apoptosis and invasion of gastric cancer 7901 cells was determined by means of the RNA interference (RNAi) of hPOT1 mRNA. The effects of hPOT1 RNAi on the expression of hPinX1 and hTERT were detected with western blotting.
  
  
  RESULTS
  The hPOT1 MOD was progressively increased from the normal mucosa to intestinal metaplasia, dysplasia, and gastric cancer. An increased hPOT1 expression significantly correlated with tumour serosal invasion, node metastasis and advanced stage. Transfection of hPOT1 siRNA into SGC-7901 cells led to a decrease in cell proliferation, colony formation and invasion, and also an increase of apoptosis. An up-regulation of hPinX1 and down-regulation of hTERT were found in gastric cancer cells with hPOT1 siRNA.
  
  
  CONCLUSIONS
  Increased hPOT1 expression is associated with an advanced tumour stage. hPOT1 RNAi inhibits proliferation and invasion, and induces apoptosis of gastric cancer cells. The effects of hPOT1 RNAi seem to be functionally linked to up-regulation of PinX1 and down-regulation of hTERT.
authors.affiliation: Department of Gastroenterology, Southwest Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Shun-Mei
authors.initials: SM
authors.lastname: Wan
authors.forename: Jun
authors.initials: J
authors.lastname: Tie
authors.forename: Ya-Fei
authors.initials: YF
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.forename: Liu-Qin
authors.initials: LQ
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Shi-Hai
authors.initials: SH
authors.lastname: Xia
authors.forename: Shi-Ming
authors.initials: SM
authors.lastname: Yang
authors.forename: Rong-Quan
authors.initials: RQ
authors.lastname: Wang
authors.forename: Dian-Chun
authors.initials: DC
authors.lastname: Fang
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D018014:Gene Transfer Techniques; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D034622:RNA Interference / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000502:physiology; D000089804:Shelterin Complex; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D019098:Telomerase / Q000378:metabolism; D034501:Telomere-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D018797:Cell Cycle Proteins; C440808:PINX1 protein, human; C440849:POT1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D025521:Tumor Suppressor Proteins; C509186:TERT protein, human; D019098:Telomerase