ZHX2 Inhibits SREBP1c-Mediated  &lt;i&gt;De Novo&lt;/i&gt; Lipogenesis in Hepatocellular Carcinoma  &lt;i&gt;via&lt;/i&gt; miR-24-3p

Yu, Xiaowen; Lin, Qinghai; Wu, Zhuanchang; Zhang, Yankun; Wang, Tixiao; Zhao, Songbai; Song, Xiaojia; Chen, Chaojia; Wang, Zehua; Xu, Leiqi; Li, Chunyang; Gao, Lifen; Liang, Xiaohong; Yue, Xuetian; Ma, Chunhong

doi:10.2139/ssrn.3546033

Cited by 11 publications

(18 citation statements)

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“…As an HCCassociated tumor suppressor, zinc fingers and homeoboxes 2 (ZHX2) is negatively associated with SREBP-1c in HCC cell lines and human specimens. ZHX2 can increase miRNA-24-3p at the transcription level to induce SREBP-1c degradation for the suppression of HCC progression (94). A member of the acyl-CoA synthetase (ACS) family, acyl CoA synthetase 4 (ACSL4) has been identified as an oncogene and a novel marker of alphafetoprotein-high subtype HCC.…”

Section: Hepatocellular Carcinomamentioning

confidence: 99%

Targeting SREBP-1-Mediated Lipogenesis as Potential Strategies for Cancer

2022

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Sterol regulatory element binding protein-1 (SREBP-1), a transcription factor with a basic helix–loop–helix leucine zipper, has two isoforms, SREBP-1a and SREBP-1c, derived from the same gene for regulating the genes of lipogenesis, including acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase. Importantly, SREBP-1 participates in metabolic reprogramming of various cancers and has been a biomarker for the prognosis or drug efficacy for the patients with cancer. In this review, we first introduced the structure, activation, and key upstream signaling pathway of SREBP-1. Then, the potential targets and molecular mechanisms of SREBP-1-regulated lipogenesis in various types of cancer, such as colorectal, prostate, breast, and hepatocellular cancer, were summarized. We also discussed potential therapies targeting the SREBP-1-regulated pathway by small molecules, natural products, or the extracts of herbs against tumor progression. This review could provide new insights in understanding advanced findings about SREBP-1-mediated lipogenesis in cancer and its potential as a target for cancer therapeutics.

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Section: Hepatocellular Carcinomamentioning

confidence: 99%

Targeting SREBP-1-Mediated Lipogenesis as Potential Strategies for Cancer

2022

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“…[12,32] In particular, the suppressive role of ZHX2 in HCC has been widely appreciated. [14,[33][34][35][36][37] NASH is an established risk factor of HCC [38,39] ; thus, it is of clinical and scientific interest to explore the role of ZHX2 in the pathogenesis of NASH, which remains unknown. The current study indicated that ZHX2 was decreased during the development of NASH.…”

Section: Discussionmentioning

confidence: 99%

The transcription factor zinc fingers and homeoboxes 2 alleviates NASH by transcriptional activation of phosphatase and tensin homolog

et al. 2022

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Background and Aims: NASH, which is a common clinical condition predisposing to advanced liver diseases, has become a worldwide epidemic. A large and growing unmet therapeutic need for this condition reflects incomplete understanding of its pathogenesis. In the current study, we identified a transcription factor, zinc fingers and homeoboxes 2 (ZHX2), in hepatocytes as a protective factor against steatohepatitis. Approach and Results:We found that hepatic ZHX2 was significantly suppressed in NASH models and steatotic hepatic cells. Hepatocyte-specific ablation of ZHX2 exacerbated NASH-related phenotypes in mice, including lipid accumulation, enhanced inflammation, and hepatic fibrosis. Conversely, hepatocyte-specific overexpression of ZHX2 significantly alleviated the progression of NASH in an experimental setting. Integrated analysis of transcriptomic profiling and chromatin immunoprecipitation sequencing data demonstrated that the phosphatase and tensin homolog (PTEN) was a target gene of ZHX2 in hepatocyte. ZHX2 bound to the promoter of PTEN gene and subsequently promoted the transcription of PTEN, which mediated the beneficial role of ZHX2 against NASH. Conclusions:The current findings demonstrate a protective role of ZHX2 against NASH progression by transcriptionally activating PTEN. These findings shed light on the therapeutic potential of targeting ZHX2 for treating NASH and related metabolic disorders.

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“…During the rapid proliferation of tumor cells, HDL-C decreases, thus preventing the loss of the intracellular cholesterol pool. The inhibition of SREBPs by small-molecule drugs such as fatostatin and microRNAs has been widely reported to exert multiple antitumor effects in various cancers (144)(145)(146) (Table 1).…”

Section: Targeting Lipid Metabolismmentioning

confidence: 99%

Metabolic Reprogramming in Hematologic Malignancies: Advances and Clinical Perspectives

Wang

Zhou

2022

Cancer Research

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Metabolic reprogramming is a hallmark of cancer progression. Metabolic activity supports tumorigenesis and tumor progression, allowing cells to uptake essential nutrients from the environment and use the nutrients to maintain viability and support proliferation. The metabolic pathways of malignant cells are altered to accommodate increased demand for energy, reducing equivalents, and biosynthetic precursors. Activated oncogenes coordinate with altered metabolism to control cell-autonomous pathways, which can lead to tumorigenesis when abnormalities accumulate. Clinical and preclinical studies have shown that targeting metabolic features of hematological malignancies is an appealing therapeutic approach. This review provides a comprehensive overview of the mechanisms of metabolic reprogramming in hematologic malignancies and potential therapeutic strategies to target cancer metabolism.

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ZHX2 Inhibits SREBP1c-Mediated <i>De Novo</i> Lipogenesis in Hepatocellular Carcinoma <i>via</i> miR-24-3p

Cited by 11 publications

References 0 publications

Targeting SREBP-1-Mediated Lipogenesis as Potential Strategies for Cancer

Targeting SREBP-1-Mediated Lipogenesis as Potential Strategies for Cancer

The transcription factor zinc fingers and homeoboxes 2 alleviates NASH by transcriptional activation of phosphatase and tensin homolog

Metabolic Reprogramming in Hematologic Malignancies: Advances and Clinical Perspectives

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