title: PACE4 regulates apoptosis in human prostate cancer cells via endoplasmic reticulum stress and mitochondrial signaling pathways.
abstract: BACKGROUND
  PACE4 is a proprotein convertase capable of processing numerous substrates involved in tumor growth, invasion, and metastasis. However, the precise role of PACE4 during prostate cancer cell apoptosis has not been reported.
  
  
  METHODS
  In the present study, human prostate cancer cell lines DU145, LNCaP, and PC3 were transfected with PACE4 small interfering (si)RNA to investigate the underlying mechanisms of apoptosis.
  
  
  RESULTS
  We revealed that PACE4 siRNA exhibited antitumor activity by inducing apoptosis, as determined by Cell Counting Kit-8 (CCK-8), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltet-razolium bromide (MTT) assay, cell cycle analysis, Hoechst staining, caspase-3/7 activity, and western blot analysis. In addition, PACE4 siRNA significantly increased the ratio of Bax/Bcl-2, which led to the release of cytochrome c. Moreover, PACE4 siRNA also induced endoplasmic reticulum stress by increasing the expression of GRP78, GRP94, p-PERK, and p-eIF2α. The ratio of Bax/Bcl-2 and GRP78 were also increased in PACE4 gene knockdown prostate cancer cells compared with the control cells.
  
  
  CONCLUSIONS
  These data demonstrate that PACE4 siRNA may exert its antitumor activity through mitochondrial and endoplasmic reticulum stress signaling pathways, indicating it may be a novel therapeutic target for prostate cancer.
authors.affiliation: Department of Urology, Air Force General Hospital of People's Liberation Army, Beijing, People's Republic of China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Department of Urology, Air Force General Hospital of People's Liberation Army, Beijing, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Urology, Air Force General Hospital of People's Liberation Army, Beijing, People's Republic of China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Hong
authors.affiliation: Department of Urology, Air Force General Hospital of People's Liberation Army, Beijing, People's Republic of China.
authors.forename: Jingmin
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Urology, Air Force General Hospital of People's Liberation Army, Beijing, People's Republic of China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Mu
authors.affiliation: Department of Urology, Air Force General Hospital of People's Liberation Army, Beijing, People's Republic of China.
authors.forename: Jianye
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Urology, Air Force General Hospital of People's Liberation Army, Beijing, People's Republic of China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Sheng
authors.affiliation: Department of Urology, Air Force General Hospital of People's Liberation Army, Beijing, People's Republic of China.
authors.forename: Heqing
authors.initials: H
authors.lastname: Guo
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D043484:Proprotein Convertases / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D034741:RNA, Small Interfering / Q000008:administration & dosage; D012697:Serine Endopeptidases / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D034741:RNA, Small Interfering; D045304:Cytochromes c; C080654:PCSK6 protein, human; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
keywords: Bax/Bcl-2; GRP78; gene knockdown; small interfering RNA; tumor growth