title: Upregulated TRIO expression correlates with a malignant phenotype in human hepatocellular carcinoma.
abstract: Triple functional domain protein (TRIO) is an evolutionarily conserved Dbl family guanine nucleotide exchange factors (GEFs) involved in cell proliferation and progression of some types of cancer. However, the expression and prognostic role of TRIO in hepatocellular carcinoma (HCC) have not yet been determined. Therefore, we attempted to determine the impact of TRIO on the clinical outcome of HCC patients to further identify its role in HCC. TRIO expression was examined using quantitative real-time PCR (qRT-PCR) and Western blotting in nonmalignant liver cells, HCC cells, and 93 paired of HCC tissues and adjacent noncancerous tissues. Statistical analyses were used to assess associations between TRIO expression and clinicopathological and prognostic factors. Small interfering RNA (siRNA)-mediated TRIO inhibition was performed in Hep3B and Huh7 cells to elucidate its roles in HCC. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was employed to measure cell proliferation, and apoptosis assay was analyzed by flow cytometry, respectively. Adhesion and transwell invasion assay were performed to determine the invasion ability of HCC cells in vitro. TRIO was significantly upregulated in the HCC cell lines and tissues compared with the nonmalignant liver cells and adjacent noncancerous liver tissues. In addition, high TRIO expression level associated with lymph node metastasis (P = 0.0183), clinical tumor node metastasis (TNM) stage (P = 0.0.0106), and decrease in overall survival (OS) (P = 0.017). Knockdown of TRIO on Hep3B and Huh7 cell lines suppressed cell proliferation and migration and induced apoptosis. Furthermore, silencing TRIO expression led to decrease of ras-related C3 botulinum toxin substrate 1 (Rac1), p-P38, B cell lymphoma 2 (BCL-2), and matrix metallopeptidase 9 (MMP-9). Our results demonstrated that TRIO protein expression is elevated and associated with a worse over survival rates in patients with HCC. Aberrant expression of TRIO might play an important role in HCC through promoting cell proliferation and invasion, and TRIO may be a novel therapeutic target for the treatment of HCC.
authors: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China. wangbinwxa@163.com.
authors: Bin
authors: B
authors: Wang
authors: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China. summer-mer-tea@163.com.
authors: JiaQing
authors: J
authors: Fang
authors: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China. quleiline@hotmail.com.
authors: Lei
authors: L
authors: Qu
authors: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China. caozhongwei@medmail.com.cn.
authors: Zhongwei
authors: Z
authors: Cao
authors: Department of General Surgery, Shanghai Sijing Hospital, 389 Sitong Road, Shanghai, 201601, China. lz203154@163.com.
authors: JianGuo
authors: J
authors: Zhou
authors: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China. lhzdeng@126.com.
authors: Biao
authors: B
authors: Deng
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020662:Guanine Nucleotide Exchange Factors / Q000096:biosynthesis* / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D020662:Guanine Nucleotide Exchange Factors; D017346:Protein Serine-Threonine Kinases; C099628:TRIO protein, human
keywords: Apoptosis; Cell adhesion; Cell invasion; Cell proliferation; HCC; Prognosis; TRIO