PMID- 36969886
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230328
IS  - 2310-8819 (Electronic)
IS  - 2225-0719 (Print)
IS  - 2225-0719 (Linking)
VI  - 11
IP  - 3
DP  - 2023 Jun 28
TI  - STX5 Inhibits Hepatocellular Carcinoma Adhesion and Promotes Metastasis by 
      Regulating the PI3K/mTOR Pathway.
PG  - 572-583
LID - 10.14218/JCTH.2022.00276 [doi]
AB  - BACKGROUND AND AIMS: Syntaxin 5 (STX5) is a member of the syntaxin or 
      target-soluble SNAP receptor (t-SNARE) family and plays a critical role in 
      autophagy. However, its function and molecular mechanism in tumor cell migration 
      are still unknown. The role of STX5 in influencing hepatocellular carcinoma (HCC) 
      is an important topic in our research. METHODS: By using quantitative reverse 
      transcription polymerase chain reaction (qPCR), western blotting, and 
      immunohistochemical analysis of RNA and protein in tissues, we comprehensively 
      evaluated data sets from public databases and clinical patient cohorts for STX5. 
      The correlation of STX5 expression with the clinicopathological characteristics 
      of HCC patients were assessed. In addition, we predicted signal pathways from 
      differentially expressed genes (DEGs) and the Cancer Genome Atlas (TCGA) 
      databases, and confirmed the prediction using integrated transcriptome and 
      RNA-seq. We further investigated the underlying mechanisms of STX5 in the 
      migration and adhesion of HCC cells both in vitro and in vivo. RESULTS: In the 
      TCGA dataset and our patient cohort, STX5 levels were significantly higher in HCC 
      tissues than in adjacent normal liver tissues. At the same time, high expression 
      of STX5 predicted worse prognosis in patients with liver cancer. High expression 
      of STX5 indicates the decrease of adhesion and the increase of migration of HCC 
      cells, and the conversion of epithelial-mesenchymal transition (EMT) in vitro via 
      PI3K/mTOR pathway activation. Conversely, when Sirolimus, a phosphoinositide 
      3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) inhibitor acts on 
      cells simultaneously, STX5 overexpression-mediated enhancement of HCC metastasis 
      is reversed. Double-negative regulation of STX5 and mTOR further enhanced the 
      inhibitory effect of STX5 on HCC metastasis. In vivo, STX5 knockdown inhibited 
      the metastasis of HCC cells. CONCLUSIONS: Our study demonstrates a novel research 
      result that STX5 promotes HCC metastasis through PI3K/mTOR pathway. We believe 
      that combined inhibition of STX5 and mTOR is a potential treatment for 
      effectively prolonging patient survival and inhibiting HCC metastasis.
CI  - (c) 2023 Authors.
FAU - Zhang, Bin
AU  - Zhang B
AUID- ORCID: 0000-0001-7191-334X
AD  - Key Laboratory of Marine Drugs, Ministry of Education School of Medicine & 
      Pharmacy, Ocean University of China, Qingdao, Shandong, China.
AD  - Organ Transplantation Center, The Affiliated Hospital of Qingdao University, 
      Qingdao, Shandong, China.
FAU - Zhao, Ziyin
AU  - Zhao Z
AUID- ORCID: 0000-0002-7358-6124
AD  - Organ Transplantation Center, The Affiliated Hospital of Qingdao University, 
      Qingdao, Shandong, China.
FAU - Wang, Youpeng
AU  - Wang Y
AUID- ORCID: 0000-0002-6453-4234
AD  - Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of 
      Qingdao University, Qingdao, Shandong, China.
FAU - Guo, Tingting
AU  - Guo T
AUID- ORCID: 0000-0002-3384-1071
AD  - Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of 
      Qingdao University, Qingdao, Shandong, China.
FAU - He, Mingyang
AU  - He M
AUID- ORCID: 0000-0003-4133-7016
AD  - Organ Transplantation Center, The Affiliated Hospital of Qingdao University, 
      Qingdao, Shandong, China.
FAU - Guan, Ge
AU  - Guan G
AUID- ORCID: 0000-0003-3696-3338
AD  - Organ Transplantation Center, The Affiliated Hospital of Qingdao University, 
      Qingdao, Shandong, China.
FAU - Peng, Pai
AU  - Peng P
AUID- ORCID: 0000-0002-3135-5600
AD  - Organ Transplantation Center, The Affiliated Hospital of Qingdao University, 
      Qingdao, Shandong, China.
FAU - Cai, Jinzhen
AU  - Cai J
AD  - Organ Transplantation Center, The Affiliated Hospital of Qingdao University, 
      Qingdao, Shandong, China.
FAU - Zhang, Bingyuan
AU  - Zhang B
AD  - Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of 
      Qingdao University, Qingdao, Shandong, China.
FAU - Liu, Xutao
AU  - Liu X
AD  - Samueli School of Engineering, University of California Los Angeles, Los Angeles, 
      CA, USA.
FAU - Song, Qiaoling
AU  - Song Q
AUID- ORCID: 0000-0003-1389-9433
AD  - Key Laboratory of Marine Drugs, Ministry of Education School of Medicine & 
      Pharmacy, Ocean University of China, Qingdao, Shandong, China.
LA  - eng
PT  - Journal Article
DEP - 20230109
PL  - United States
TA  - J Clin Transl Hepatol
JT  - Journal of clinical and translational hepatology
JID - 101649815
PMC - PMC10037512
OTO - NOTNLM
OT  - Epithelial-mesenchymal transition
OT  - Hepatocellular carcinoma
OT  - PI3K/mTOR
OT  - Syntaxin 5
COIS- The authors have no conflict of interests related to this publication.
EDAT- 2023/03/28 06:00
MHDA- 2023/03/28 06:01
PMCR- 2023/01/09
CRDT- 2023/03/27 03:44
PHST- 2022/06/05 00:00 [received]
PHST- 2022/07/21 00:00 [revised]
PHST- 2022/08/15 00:00 [accepted]
PHST- 2023/03/27 03:44 [entrez]
PHST- 2023/03/28 06:00 [pubmed]
PHST- 2023/03/28 06:01 [medline]
PHST- 2023/01/09 00:00 [pmc-release]
AID - JCTH.2022.00276 [pii]
AID - 10.14218/JCTH.2022.00276 [doi]
PST - ppublish
SO  - J Clin Transl Hepatol. 2023 Jun 28;11(3):572-583. doi: 10.14218/JCTH.2022.00276. 
      Epub 2023 Jan 9.