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Tripartite motif 8 (TRIM8) is an E3 ligase that plays dual roles in various tumor types. The biological effects and underlying mechanism of TRIM8 in hepatocellular carcinoma (HCC) remain unknown. Hepatocyte nuclear factor 1α (HNF1α) is a key transcriptional factor that plays a significant role in regulating hepatocyte differentiation and liver function. The reduced expression of HNF1α is a critical event in the development of HCC, but the underlying mechanism for its degradation remains elusive. In this study, we discovered that the expression of TRIM8 was upregulated in HCC tissues, and was positively correlated with aggressive tumor behavior of HCC and shorter survival of HCC patients. Overexpression of TRIM8 promoted the proliferation, colony formation, invasion, and migration of HCC cells, while TRIM8 knockdown or knockout exerted the opposite effects. RNA sequencing revealed that TRIM8 knockout suppresses several cancer-related pathways, including Wnt/β-catenin and TGF-β signaling in HepG2 cells. TRIM8 directly interacts with HNF1α, promoting its degradation by catalyzing polyubiquitination on lysine 197 in HCC cells. Moreover, the cancer-promoting effects of TRIM8 in HCC were abolished by the HNF1α-K197R mutant in vitro and in vivo. These data demonstrated that TRIM8 plays an oncogenic role in HCC progression through mediating the ubiquitination of HNF1α and promoting its protein degradation, and suggests targeting TRIM8-HNF1α may provide a promising therapeutic strategy of HCC.
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http://dx.doi.org/10.1038/s41419-024-06819-y | DOI Listing |
Front Oncol
December 2024
Department of Hepatobiliary and Pancreatic Surgery I, General Surgery Center, The First Hospital of Jilin University, Changchun, China.
Primary liver cancer, predominantly hepatocellular carcinoma (HCC), is a leading cause of cancer-related mortality. Tumor thrombus (TT) in the inferior vena cava (IVC) or right atrium (RA) significantly worsens prognosis. We present four cases of male patients (average age 57) with HCC and TT extending into the IVC/RA, treated at our center.
View Article and Find Full Text PDFFront Oncol
December 2024
The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China.
Background: Since the emergence of the hot topic of "ferroptosis," numerous studies have explored its role in hepatocellular carcinoma (HCC), revealing its significance in the disease's pathogenesis, progression, and treatment. However, there remains a significant gap in the quantitative analysis of ferroptosis in HCC. Therefore, this study aims to comprehensively assess the research progress and evolution in this field through bibliometric and citation analysis.
View Article and Find Full Text PDFCureus
November 2024
Surgery, Nippon Medical School, Tokyo, JPN.
While orbital floor metastasis from hepatocellular carcinoma (HCC) has been reported, ocular (eyeball) metastasis is exceedingly rare. Most ocular metastases originate from breast or lung cancer. In this article, we present the case of a 65-year-old man diagnosed with HCC with central necrosis (cT3N0M0, stage III) based on characteristic imaging findings.
View Article and Find Full Text PDFBackground: This case series evaluated the clinical impact and significant technical points of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) using the smaller drug-eluting bead (DEB) M1 (DC Bead M1; 70-150 µm).
Methods: We evaluated 12 patients and 14 HCC nodules treated with DEB-TACE using the DC Bead M1 (named DEM1-TACE). In addition to evaluating the early treatment efficacy for each treated node after DEM1-TACE, the study also used interventional radiology (IVR)- computed tomography (CT) to focus on the presence or absence of retention of the homogeneous contrast medium in target nodules after DEM1-TACE as a predictor of a good treatment response.
Front Pharmacol
December 2024
Precision Pharmacy and Drug Development Center, Department of Pharmacy, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China.
Introduction: Hepatocellular carcinoma (HCC), the third leading cancer mortality worldwide, shows rising incidence. The mitochondria in HCC cells are prone to damage from metabolic stress and oxidative stress, necessitating heightened mitophagy for mitochondrial homeostasis and cell survival. Thus, mitophagy inhibition is a promising HCC therapy.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!