title: Expression and clinical significance of HMGB1 in human liver cancer:             Knockdown inhibits tumor growth and metastasis in vitro and in vivo.
abstract: The high-mobility group box 1 (HMGB1) signaling pathway plays a crucial             role in tumorigenesis and progression of many malignant cancers. The present study             aimed to investigate the expression and clinical significance of HMGB1 in human             primary liver cancer, and further explore the molecular mechanisms of HMGB1 in             tumor growth and metastasis. Forty cases of human liver cancer and normal liver             tissues were collected. The expression of HMGB1 was assessed using RT-PCR and             western blot assays in biopsy samples. The HMGB1 pathway in vitro was blocked             using transfection of the recombinant small hairpin RNA adenovirus vector rAd5-HMGB1             into the human liver cancer cell line SMMC-7721. The expression of HMGB1, phosphorylated             AKT (p-AKT), Ki-67 and matrix metallopeptidase-2 (MMP-2) was detected by Real-PCR             and western blot assays. Cell proliferative activities and metastatic capability             were determined by MTT and Transwell assays. Cell cycle distribution and apoptosis             were detected by flow cytometry. A subcutaneous xenograft tumor model was established,             validating the effects of rAd5-HMGB1 on tumor growth in vivo. As a consequence,             HMGB1 was found to be highly expressed in liver cancer compared with normal tissues,             and was positively associated with pathological grade and distant metastases of             liver cancer. Knockdown of HMGB1 downregulated the expression of p-AKT, Ki-67             and MMP-2, inhibited the proliferative activities and metastatic potential of             SMMC-7721 cells, induced cell cycle arrest and apoptosis, and slowed the growth             of xenograft tumors. Altogether, the expression of HMGB1 is closely correlated             with pathological grade and distant metastases of liver cancer, and knockdown             of HMGB1 inhibits liver cancer growth and metastasis, suggesting that HMGB1 may             be involved in liver cancer development and progression through AKT-mediated regulation             of Ki-67 and MMP-2 expression, and represent a potential therapeutic target for             this aggressive malignancy.
authors.affiliation: Department of General Surgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.
authors.forename: Ya-Dong
authors.initials: YD
authors.lastname: Dong
authors.forename: Long
authors.initials: L
authors.lastname: Cui
authors.forename: Cheng-Hong
authors.initials: CH
authors.lastname: Peng
authors.forename: Dong-Feng
authors.initials: DF
authors.lastname: Cheng
authors.forename: Bao-San
authors.initials: BS
authors.lastname: Han
authors.forename: Fang
authors.initials: F
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002448:Cell Adhesion; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D024243:HMGB1 Protein; D012333:RNA, Messenger