title: GRAM domain-containing protein 1A (GRAMD1A) promotes the expansion of hepatocellular carcinoma stem cell and hepatocellular carcinoma growth through STAT5.
abstract: Hepatocellular carcinoma (HCC) is the leading cause for cancer death worldwide, new prognostic factors and targets are critical for HCC treatment. Here, we found GRAMD1A was upregulated in HCC tissues, patients with high GRAMD1A levels had poor outcome, statistical analyses found GRAMD1A expression was positively correlated with pathologic differentiation and survival or mortality. It was an unfavorable prognostic factor for HCC patients. Functional analyses revealed GRAMD1A contributed to the self-renewal of HCC stem cells, resistance to chemotherapy and tumor growth of HCC determined by hepatosphere formation assay, side population (SP) analysis, TUNEL assay, soft agar growth ability assay and tumor growth model in vivo. Mechanism analyses found signal transducer and activator of transcription 5 (STAT5) was the target of GRAMD1A, GRAMD1A regulated the target genes of STAT5 and the transcriptional activity of STAT5. Inhibition of STAT5 in indicated HCC cells overexpressing GRAMD1A suppressed the effects of GRAMD1A on the self-renewal of HCC stem cell, resistance to chemotherapy and tumor growth, suggesting GRAMD1A promoted the self-renewal of HCC stem cells and the development of HCC by increasing STAT5 level. GRAMD1A might be a useful biomarker and target for HCC.
authors: Department of Hepatic Surgery, Liver Transplant Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, P. R. China.|Liver Transplantation Center of Sun Yat-sen University, Guangzhou 510630, P. R. China.|Organ Transplantation Institute of Guangdong Province, Guangzhou 510630, P. R. China.
authors: Binsheng
authors: B
authors: Fu
authors: Department of Hepatic Surgery, Liver Transplant Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, P. R. China.|Liver Transplantation Center of Sun Yat-sen University, Guangzhou 510630, P. R. China.|Organ Transplantation Institute of Guangdong Province, Guangzhou 510630, P. R. China.
authors: Wei
authors: W
authors: Meng
authors: Department of Hepatic Surgery, Liver Transplant Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, P. R. China.|Liver Transplantation Center of Sun Yat-sen University, Guangzhou 510630, P. R. China.|Organ Transplantation Institute of Guangdong Province, Guangzhou 510630, P. R. China.
authors: Hui
authors: H
authors: Zhao
authors: Department of Medical Imaging, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, P. R. China.
authors: Bing
authors: B
authors: Zhang
authors: Department of Hepatic Surgery, Liver Transplant Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, P. R. China.|Liver Transplantation Center of Sun Yat-sen University, Guangzhou 510630, P. R. China.|Organ Transplantation Institute of Guangdong Province, Guangzhou 510630, P. R. China.
authors: Hui
authors: H
authors: Tang
authors: Department of Medical Oncology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, P. R. China.
authors: Ying
authors: Y
authors: Zou
authors: Department of Hepatic Surgery, Liver Transplant Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, P. R. China.|Liver Transplantation Center of Sun Yat-sen University, Guangzhou 510630, P. R. China.|Organ Transplantation Institute of Guangdong Province, Guangzhou 510630, P. R. China.
authors: Jia
authors: J
authors: Yao
authors: Department of Medical Oncology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, P. R. China.
authors: Heping
authors: H
authors: Li
authors: Department of Hepatic Surgery, Liver Transplant Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, P. R. China.|Liver Transplantation Center of Sun Yat-sen University, Guangzhou 510630, P. R. China.|Organ Transplantation Institute of Guangdong Province, Guangzhou 510630, P. R. China.
authors: Tong
authors: T
authors: Zhang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D000066673:Cell Self Renewal / Q000502:physiology; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019694:Hepatitis B, Chronic / Q000150:complications; D064593:Heterografts; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000473:pathology; D050799:STAT5 Transcription Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: C000597919:GRAMD1A protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D050799:STAT5 Transcription Factor