BDH2 is downregulated in hepatocellular carcinoma and acts as a tumor suppressor regulating cell apoptosis and autophagy

Liang, Hao; Zhang, Xiong; Li, Ruixi; Hu, Kunpeng; Cao, Mingbo; Yang, Jiarui; Zhong, Zhaozhong; Jia, Changchang; Yao, Zhicheng; Deng, Meihai

doi:10.7150/jca.32022

Cited by 22 publications

(19 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AMPK, MAPK/Erk1/2, and PI3K/Akt/mTOR signalling pathways are classic apoptosis and autophagy pathways [28][29][30]. Previous studies have shown that BDH2 inhibits HCC cell growth, proliferation, and migration by inducing apoptosis and autophagy [31]. However, the specific molecular mechanisms of BDH2-induced apoptosis and autophagy remained unclear.…”

Section: Discussionmentioning

confidence: 99%

BDH2 triggers ROS-induced cell death and autophagy by promoting Nrf2 ubiquitination in gastric cancer

Liu

Feng

et al. 2020

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Background: 3-Hydroxy butyrate dehydrogenase 2 (BDH2) is a short-chain dehydrogenase/reductase family member that plays a key role in the development and pathogenesis of human cancers. However, the role of BDH2 in gastric cancer (GC) remains largely unclear. Our study aimed to ascertain the regulatory mechanisms of BDH2 in GC, which could be used to develop new therapeutic strategies. Methods: Western blotting, immunohistochemistry, and RT-PCR were used to investigate the expression of BDH2 in GC specimens and cell lines. Its correlation with the clinicopathological characteristics and prognosis of GC patients was analysed. Functional assays, such as CCK-8 and TUNEL assays, transmission electron microscopy, and an in vivo tumour growth assay, were performed to examine the proliferation, apoptosis, and autophagy of GC cells. Related molecular mechanisms were clarified by luciferase reporter, coimmunoprecipitation, and ubiquitination assays. Results: BDH2 was markedly downregulated in GC tissues and cells, and the low expression of BDH2 was associated with poor survival of GC patients. Functionally, BDH2 overexpression significantly induced apoptosis and autophagy in vitro and in vivo. Mechanistically, BDH2 promoted Keap1 interaction with Nrf2 to increase the ubiquitination level of Nrf2. Ubiquitination/degradation of Nrf2 inhibited the activity of ARE to increase accumulation of reactive oxygen species (ROS), thereby inhibiting the phosphorylation levels of Akt Ser473 and mTOR Ser2448. Conclusions: Our study indicates that BDH2 is an important tumour suppressor in GC. BDH2 regulates intracellular ROS levels to mediate the PI3K/Akt/mTOR pathway through Keap1/Nrf2/ARE signalling, thereby inhibiting the growth of GC.

show abstract

Section: Discussionmentioning

confidence: 99%

BDH2 triggers ROS-induced cell death and autophagy by promoting Nrf2 ubiquitination in gastric cancer

Liu

Feng

et al. 2020

J Exp Clin Cancer Res

View full text Add to dashboard Cite

show abstract

“…Inclusion criteria: (1) studies were focused on the correlation between leptin or AdipoQ levels and HCC risk, and provided full text and complete data in HCC patients and cancer-free controls (CFC), or (2) investigated the correlation between AdipoQ or leptin levels and the prognosis of HCC, and provided sufficient information to get the hazard ratio (HR) and 95% confidence intervals (CIs). Exclusion criteria: conference abstracts, case reports, comments, review, and experimental animal studies were excluded.…”

Section: Study Selection Criteriamentioning

confidence: 99%

The association of leptin and adiponectin with hepatocellular carcinoma risk and prognosis: a combination of traditional, survival, and dose-response meta-analysis

Zhang

Yuan

et al. 2020

BMC Cancer

View full text Add to dashboard Cite

Background An increasing number of studies have focused on the association between leptin, adiponectin levels and the risk as well as the prognosis of hepatocellular carcinoma. However, the reported results are conflicting. Methods A meta-analysis was performed to assess the correlation between leptin, adiponectin levels and risk and prognosis of hepatocellular carcinoma (CRD42020195882). Through June 14, 2020, PubMed, Cochrane Library and EMBASE databases were searched, including references of qualifying articles. Titles, abstracts, and main texts were reviewed by at least 2 independent readers. Stata 16.0 was used to calculate statistical data. Results Thirty studies were included in this meta-analysis and results showed that hepatocellular carcinoma group had significantly higher leptin levels than the cancer-free control group (SMD = 1.83, 95% CI (1.09, 2.58), P = 0.000), the healthy control group (SMD = 4.32, 95% CI (2.41, 6.24), P = 0.000) and the cirrhosis group (SMD = 1.85, 95% CI (0.70, 3.01), P = 0.002). Hepatocellular carcinoma group had significantly higher adiponectin levels than the healthy control group (SMD = 1.57, 95% CI (0.37, 2.76), P = 0.010), but no statistical difference compared with the cancer-free control group (SMD = 0.24, 95% CI (− 0.35, 0.82), P = 0.430) and the cirrhosis group (SMD = − 0.51, 95% CI (− 1.30, 0.29), P = 0.213). The leptin rs7799039 polymorphism was associated with increased risk of hepatocellular carcinoma (G vs A: OR = 1.28, 95% CI (1.10, 1.48), P = 0.002). There were linear relationships between adiponectin levels and the risk of hepatocellular carcinoma (OR = 1.066, 95% CI (1.03, 1.11), P = 0.001). In addition, the results showed that high/positive expression of adiponectin was significantly related to lower overall survival in hepatocellular carcinoma patients (HR = 1.70, 95% CI (1.22, 2.37), P = 0.002); however, there was no significantly association between the leptin levels and overall survival (HR = 0.92, 95% CI (0.53, 1.59), P = 0.766). Conclusion The study shows that high leptin levels were associated with a higher risk of hepatocellular carcinoma. Adiponectin levels were proportional to hepatocellular carcinoma risk, and were related to the poor prognosis.

show abstract

“…Inclusion criteria: studies (1) were focused on the correlation between leptin or AdipoQ levels and HCC risk, and provided full text and complete data in HCC patients and controls, or (2) investigate the correlation between AdipoQ or leptin levels and the prognosis of HCC, and provide su cient information to get the hazard ratio (HR) and 95% con dence intervals (CIs). Exclusion criteria: conference abstracts, case reports, comments, review, editorials, letters to the editor, and experimental animal studies were excluded.…”

Section: Study Selection Criteriamentioning

confidence: 99%

“…In 2018, hepatocellular carcinoma (HCC) became the sixth most common cancer in the world and the fourth leading cause of cancer death globally [1]. The pathogenesis of HCC is complicated and still unclear, the process is high invasion and aggression, and the prognosis is very poor [2]. HCC is generally secondary to liver cirrhosis or viral hepatitis.…”

Section: Introductionmentioning

confidence: 99%

Association of Circulating Leptin and Adiponectin with Risk and Prognosis of Hepatocellular carcinoma: A Combination of Traditional, Survival and Dose-response Meta-analysis

Li-long

Yuan

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: The association between leptin, adiponectin levels and the risk and prognosis of hepatocellular carcinoma has been investigated by a growing number of studies, but the results were controversial. Methods: We performed the meta-analysis to assess the relationships between leptin, adiponectin levels and the risk and prognosis of hepatocellular carcinoma (CRD42020195882). Through June 14, 2020, PubMed, Cochrane Library, Embase databases, Clinicaltrials, and Opengrey was searhed, including references of qualifying articles. Titles, abstracts, and articles were reviewed by at least 2 independent readers. Stata 16.0 was used to calculate statistical data. Results: Thirty studies were included in this meta-analysis and results showed that hepatocellular carcinoma group has significantly higher leptin levels than the cancer-free control group (SMD = 1.83, 95% CI (1.09, 2.58), P = 0.000) , the healthy control group (SMD = 4.32, 95% CI (2.41, 6.24), P = 0.000) and the cirrhosis group (SMD = 1.85, 95% CI (0.70, 3.01), P = 0.002). Hepatocellular carcinoma group has significantly higher adiponectin levels than the the healthy control group (SMD = 1.57, 95% CI (0.37, 2.76), P = 0.010), but no statistical difference compared with the cancer-free control group (SMD = 0.24, 95% CI (-0.35, 0.82), P = 0.430) and the cirrhosis group (SMD = -0.51, 95% CI (-1.30, 0.29), P= 0.213). The leptin rs7799039 polymorphism was associated with an increased the risk of hepatocellular carcinoma (G vs A: OR = 1.28, 95% CI (1.10, 1.48), P = 0.002). There were linear relationships between adiponectin levels and the risk of hepatocellular carcinoma (OR = 1.066, 95% CI (1.03, 1.11), P = 0.001). In addition, the results showed that high/positive expression of adiponectin was significantly related to lower overall survival in hepatocellular carcinoma patients (HR = 1.70, 95% CI (1.22, 2.37), P = 0.002); however, there was no significantly association between the leptin levels and overall survival (HR = 0.92, 95% CI (0.53, 1.59), P = 0.766). Conclusion: The study shows that high leptin levels were associated with a higher risk of hepatocellular carcinoma. Adiponectin levels were proportional to hepatocellular carcinoma risk, and were related to the poor prognosis.

show abstract

BDH2 is downregulated in hepatocellular carcinoma and acts as a tumor suppressor regulating cell apoptosis and autophagy

Cited by 22 publications

References 47 publications

BDH2 triggers ROS-induced cell death and autophagy by promoting Nrf2 ubiquitination in gastric cancer

BDH2 triggers ROS-induced cell death and autophagy by promoting Nrf2 ubiquitination in gastric cancer

The association of leptin and adiponectin with hepatocellular carcinoma risk and prognosis: a combination of traditional, survival, and dose-response meta-analysis

Association of Circulating Leptin and Adiponectin with Risk and Prognosis of Hepatocellular carcinoma: A Combination of Traditional, Survival and Dose-response Meta-analysis

Contact Info

Product

Resources

About