Accumulation of TOX high mobility group box family member 3 promotes the oncogenesis and development of hepatocellular carcinoma through the MAPK signaling pathway

© 2024 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd..

Microvascular invasion (MVI) has been widely valued in the field of liver surgery because MVI positivity indicates poor prognosis in hepatocellular carcinoma (HCC) patients. However, the potential molecular mechanism underlying the poor prognosis of MVI-positive HCC patients is unclear. Therefore, this study focused on identifying the key genes leading to poor prognosis in patients with a high degree of malignancy of HCC by examining the molecular signaling pathways in MVI-positive HCC patients. Through RNA sequencing, TOX high mobility group box family member 3 (TOX3) was demonstrated to be significantly highly expressed in MVI-positive HCC tissues, which was associated with poor prognosis. The results of in vivo and in vitro showed that TOX3 can promote the oncogenesis and development of HCC by targeting key molecules of the MAPK and EMT signaling pathways. The IP-MS results indicated that proteasome degradation of TOX3 in HCC cells is potentially mediated by a tripartite motif containing 56 (TRIM56, an E3 ligase) in HCC cells. Inhibiting TRIM56 enhances TOX3 protein levels. Overall, our study identified TOX3 as a key gene in the MAPK and EMT signaling pathways in HCC, and its overexpression confers significant proliferation and invasiveness to tumor cells.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:5

Enthalten in:

MedComm - 5(2024), 3 vom: 27. März, Seite e510

Sprache:

Englisch

Beteiligte Personen:

Peng, Yufu [VerfasserIn]
Yu, Jing [VerfasserIn]
Liu, Fei [VerfasserIn]
Tang, Leyi [VerfasserIn]
Li, Bo [VerfasserIn]
Zhang, Wei [VerfasserIn]
Chen, Kefei [VerfasserIn]
Zhang, Haili [VerfasserIn]
Wei, Yonggang [VerfasserIn]
Ma, Xuelei [VerfasserIn]
Shi, Hubing [VerfasserIn]

Links:

Volltext

Themen:

Growth and metastasis of liver cancer
Hepatocellular carcinoma
Insulin‐like growth factor binding protein 3
Journal Article
Microvascular invasion
TOX high mobility group box family member 3
Tripartite motif containing 56

Anmerkungen:

Date Revised 12.03.2024

published: Electronic-eCollection

Citation Status PubMed-not-MEDLINE

doi:

10.1002/mco2.510

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369531345