Hepatocyte-Specific Knock-Out of Nfib Aggravates Hepatocellular Tumorigenesis via Enhancing Urea Cycle

Zhou, Li; Wang, Qingliang; Mao, Lin-Hong; Chen, Siyuan; Yang, Zihan; Li, Xue; Gao, Yuhua; Li, Xiaoqin; Zhou, Zhihang; He, Song

doi:10.3389/fmolb.2022.875324

Cited by 5 publications

(5 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our previous research found that NFIB was elevated in acid-adapted CRC cells 11 and promoted tumor cell proliferation, invasion, and drug resistance in sorafenib-resistant hepatocellular carcinoma (HCC) cells 12 . However, we also found that hepatocyte-specific knockout of NFIB facilitated the occurrence of HCC 13 . Therefore, the role of NFIB in the tumor is complex, and its role in CRC needs to be further clarified.…”

Section: Introductionmentioning

confidence: 55%

Downregulation of miR-182-5p by NFIB promotes NAD+ salvage synthesis in colorectal cancer by targeting NAMPT

Zhou¹,

Liu²,

Chen³

et al. 2023

Commun Biol

Self Cite

View full text Add to dashboard Cite

Nuclear factor I B (NFIB) plays an important role in tumors. Our previous study found that NFIB can promote colorectal cancer (CRC) cell proliferation in acidic environments. However, its biological functions and the underlying mechanism in CRC are incompletely understood. Nicotinamide adenine dinucleotide (NAD+) effectively affects cancer cell proliferation. Nevertheless, the regulatory mechanism of NAD+ synthesis in cancer remains to be elucidated. Here we show NFIB promotes CRC proliferation in vitro and growth in vivo, and down-regulation of NFIB can reduce the level of NAD+. In addition, supplementation of NAD+ precursor NMN can recapture cell proliferation in CRC cells with NFIB knockdown. Mechanistically, we identified that NFIB promotes CRC cell proliferation by inhibiting miRNA-182-5p targeting and binding to NAMPT, the NAD+ salvage synthetic rate-limiting enzyme. Our results delineate a combination of high expression of NFIB and NAMPT predicted a clinical poorest prognosis. This work provides potential therapeutic targets for CRC treatment.

show abstract

Section: Introductionmentioning

confidence: 55%

Downregulation of miR-182-5p by NFIB promotes NAD+ salvage synthesis in colorectal cancer by targeting NAMPT

Zhou¹,

Liu²,

Chen³

et al. 2023

Commun Biol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Most relevant to this study, DOCK1 upregulation was associated with HCC growth and progression [48]. HCC is one of the five most common cancers in the world [49] that, in contrast to other malignancies, tends to affect only the liver without spreading elsewhere [50]. The development of HCC is multifactorial, including a history of chronic liver disease, hepatitis B virus (HBV), hepatitis C virus (HCV) infection, and alcoholism [51].…”

Section: Discussionmentioning

confidence: 94%

The Carcinogenic Potential of Bisphenol A in the Liver Based on Transcriptomic Studies

Wiszpolska,

Lepiarczyk,

Maździarz

et al. 2023

Cancers

View full text Add to dashboard Cite

Bisphenol A (BPA) is an environmental toxin widely used in the production of polycarbonate plastics. A correlation exists between BPA tissue contamination and the occurrence of pathological conditions, including cancer. First-passage detoxification of high BPA amounts in the liver promotes hepatotoxicity and morphological alterations of this organ, but there is a lack of knowledge about the molecular mechanisms underlying these phenomena. This prompted us to investigate changes in the liver transcriptomics of 3-month-old female mice exposed to BPA (50 mg/kg) in drinking water for 3 months. Five female mice served as controls. The animals were euthanized, the livers were collected, and RNA was extracted to perform RNA-seq analysis. The multistep transcriptomic bioinformatics revealed 120 differentially expressed genes (DEGs) in the BPA-exposed samples. Gene Ontology (GO) annotations indicated that DEGs have been assigned to many biological processes, including “macromolecule modification” and “protein metabolic process”. Several of the revealed DEGs have been linked to the pathogenesis of severe metabolic liver disorders and malignant tumors, in particular hepatocellular carcinoma. Data from this study suggest that BPA has a significant impact on gene expression in the liver, which is predictive of the carcinogenic potential of this compound in this organ.

show abstract

“…Samples from animals with unclear/insufficient extent of genetic knockdown were excluded from this study. A total of 25 formalin-fixed paraffin-embedded (FFPE) blocks from KRAS [ 28 ], KRAS/adenosine kinase (Adk) [ 32 ] and KRAS/ nuclear factor IA (Nfia) [ 33 ] genetically engineered mice (GEMM) were included in this study. These mice have previously been extensively characterized and chosen for this study due to a high tumor burden including a high percentage of FCA and HCC tumor nodules [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

Vascular Remodeling Is a Crucial Event in the Early Phase of Hepatocarcinogenesis in Rodent Models for Liver Tumorigenesis

Tulessin

Sarker²,

Griger³

et al. 2022

Cells

View full text Add to dashboard Cite

The investigation of hepatocarcinogenesis is a major field of interest in oncology research and rodent models are commonly used to unravel the pathophysiology of onset and progression of hepatocellular carcinoma. HCC is a highly vascularized tumor and vascular remodeling is one of the hallmarks of tumor progression. To date, only a few detailed data exist about the vasculature and vascular remodeling in rodent models used for hepatocarcinogenesis. In this study, the vasculature of HCC and the preneoplastic foci of alteration (FCA) of different mouse models with varying genetic backgrounds were comprehensively characterized by using immunohistochemistry (CD31, Collagen IV, αSMA, Desmin and LYVE1) and RNA in situ hybridization (VEGF-A). Computational image analysis was performed to evaluate selected parameters including microvessel density, pericyte coverage, vessel size, intratumoral vessel distribution and architecture using the Aperio ImageScope and Definiens software programs. HCC presented with a significantly lower number of vessels, but larger vessel size and increased coverage, leading to a higher degree of maturation, whereas FCA lesions presented with a higher microvessel density and a higher amount of smaller but more immature vessels. Our results clearly demonstrate that vascular remodeling is present and crucial in early stages of experimental hepatocarcinogenesis. In addition, our detailed characterization provides a strong basis for further angiogenesis studies in these experimental models.

show abstract

Hepatocyte-Specific Knock-Out of Nfib Aggravates Hepatocellular Tumorigenesis via Enhancing Urea Cycle

Cited by 5 publications

References 49 publications

Downregulation of miR-182-5p by NFIB promotes NAD+ salvage synthesis in colorectal cancer by targeting NAMPT

Downregulation of miR-182-5p by NFIB promotes NAD+ salvage synthesis in colorectal cancer by targeting NAMPT

The Carcinogenic Potential of Bisphenol A in the Liver Based on Transcriptomic Studies

Vascular Remodeling Is a Crucial Event in the Early Phase of Hepatocarcinogenesis in Rodent Models for Liver Tumorigenesis

Contact Info

Product

Resources

About