Midnolin Regulates Liver Cancer Cell Growth In Vitro and In Vivo

Kweon, Soo-Mi; Kim, Gayeoun; Jeong, Y.S.; Huang, Wendong; Lee, Ju Seog; Lai, Keane K.Y.

doi:10.3390/cancers14061421

Cited by 5 publications

(6 citation statements)

References 30 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The high expression of midnolin was associated with poor overall survival and relapse‐free survival of HCC patients. Inhibition of midnolin downregulated Aldh1a1, Ttr, Lpl, Lrp1, Acsl1, Stra6 and upregulated Rbp1 and altered retinoic acid metabolism or lipid metabolism 7 . ASCL1 was a driver of cancer neuroendocrine phenotype and therapeutic resistance.…”

Section: Figurementioning

confidence: 98%

“…Midnolin (MIDN) was highly expressed in hepatocellular carcinoma (HCC) tumors compared with normal liver. 7 The high expression of midnolin was associated with poor overall survival and relapse‐free survival of HCC patients. Inhibition of midnolin downregulated Aldh1a1, Ttr, Lpl, Lrp1, Acsl1, Stra6 and upregulated Rbp1 and altered retinoic acid metabolism or lipid metabolism.…”

Section: Figurementioning

confidence: 98%

“…Midnolin (MIDN) was highly expressed in hepatocellular carcinoma (HCC) tumors compared with normal liver 7 . The high expression of midnolin was associated with poor overall survival and relapse‐free survival of HCC patients.…”

Section: Figurementioning

confidence: 99%

See 2 more Smart Citations

Midnolin‐proteasome pathway for protein degradation

Jin

2023

MedComm

View full text Add to dashboard Cite

Overexpression of immediate‐early genes (IEGs) has been linked to was associated with cancer progression and prognosis. In a recent study, Gu et al. reported the midnolin‐proteasome pathway, a novel ubiquitin‐independent proteasomal degradation. 1 The study provided the mechanism of rapid degradation for nuclear proteins with high unsteadiness. Targeting the midnolin‐proteasome pathway might be beneficial for cancer therapy.

show abstract

Section: Figurementioning

confidence: 98%

Section: Figurementioning

confidence: 98%

See 1 more Smart Citation

Midnolin‐proteasome pathway for protein degradation

Jin

2023

MedComm

View full text Add to dashboard Cite

show abstract

“…Therefore, NAC1 may have a significant impact on the advancement of HCC through the regulation of LDHA [ 16 ]. This discovery not only offers a fresh perspective on the pathogenesis of HCC, but also provides novel insights for targeted therapies against NAC1 and LDHA [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

NAC1 transcriptional activation of LDHA induces hepatitis B virus immune evasion leading to cirrhosis and hepatocellular carcinoma development

Chen,

Guo,

et al. 2024

Oncogenesis

View full text Add to dashboard Cite

Our study aimed to elucidate the molecular mechanisms underlying NAC1 (nucleus accumbens associated 1) transcriptional regulation of LDHA and its role in HBV immune evasion, thus contributing to the development of cirrhosis and hepatocellular carcinoma (HCC). Utilizing public datasets, we performed differential gene expression and weighted gene co-expression network analysis (WGCNA) on HBV-induced cirrhosis/HCC data. We identified candidate genes by intersecting differentially expressed genes with co-expression modules. We validated these genes using the TCGA database, conducting survival analysis to pinpoint key genes affecting HBV-HCC prognosis. We also employed the TIMER database for immune cell infiltration data and analyzed correlations with identified key genes to uncover potential immune escape pathways. In vitro, we investigated the impact of NAC1 and LDHA on immune cell apoptosis and HBV immune evasion. In vivo, we confirmed these findings using an HBV-induced cirrhosis model. Bioinformatics analysis revealed 676 genes influenced by HBV infection, with 475 genes showing differential expression in HBV-HCC. NAC1 emerged as a key gene, potentially mediating HBV immune escape through LDHA transcriptional regulation. Experimental data demonstrated that NAC1 transcriptionally activates LDHA, promoting immune cell apoptosis and HBV immune evasion. Animal studies confirmed these findings, linking NAC1-mediated LDHA activation to cirrhosis and HCC development. NAC1, highly expressed in HBV-infected liver cells, likely drives HBV immune escape by activating LDHA expression, inhibiting CD8 + T cells, and promoting cirrhosis and HCC development.

show abstract

“…6) Additionally, duplications in 19p13.3, which includes the MIDN locus, are associated with male infertility 7) and MIDN is involved in progression of hepatocellular carcinomas. 8) Previously, we identified MIDN as a genetic risk factor for PD by array-based genome-wide association studies of cohorts from Yamagata Prefecture in north-east Japan and Great Britain. 9,10) In the Yamagata Prefecture cohort, MIDN copy number loss was observed in 10.5% of sporadic PD patients, whereas none was observed in 100 controls.…”

Section: Introductionmentioning

confidence: 99%

Structural Variants of <i>Midnolin</i>, a Genetic Risk Factor for Parkinson’s Disease, in a Yamagata Cohort

Sato

Ishii

Obara

2023

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Parkinson's disease (PD) is a common neurodegenerative disease. We previously identified Midnolin (MIDN) to be a genetic risk factor for PD in both Yamagata (Japan) and British populations. However, the scale of our previous study was not sufficient to identify MIDN structural variants in the ascertained control of Yamagata Prefecture. We, therefore, reanalyzed MIDN variants in 3021 individuals from Yamagata Prefecture to compare with that in our previous British cohort study. MIDN copy number loss was only found in two cases (0.0662%), which was a lower frequency than that (1.64%) of the previously studied British cohort. Between the Yamagata and British groups, there was significant difference for rs3746106, located in the 5′-UTR of MIDN mRNA (p 0.0003344, odds ratio 1.143), and for rs3746107, which corresponds to Ala34 (p < 2.2 10 16 , odds ratio 5.89401). This study indicates that MIDN loss is relatively rare in the general Japanese population. Considering our previous studies that the frequency of MIDN loss is high among patients with PD (10.5 and 6.55% in Yamagata and Britain, respectively), the MIDN variants are much higher genetic risk factors for PD in a Japanese population than in a British population.

show abstract

Midnolin Regulates Liver Cancer Cell Growth In Vitro and In Vivo

Cited by 5 publications

References 30 publications

Midnolin‐proteasome pathway for protein degradation

Midnolin‐proteasome pathway for protein degradation

NAC1 transcriptional activation of LDHA induces hepatitis B virus immune evasion leading to cirrhosis and hepatocellular carcinoma development

Structural Variants of <i>Midnolin</i>, a Genetic Risk Factor for Parkinson’s Disease, in a Yamagata Cohort

Contact Info

Product

Resources

About