A Novel Oxoglutarate Dehydrogenase-Like Mediated miR-214/TWIST1 Negative Feedback Loop Inhibits Pancreatic Cancer Growth and Metastasis

Liu, Yao; Meng, F.; Wang, Jiabei; Li, Mingyang; Yang, Guangchao; Song, Ran; Zheng, Tongsen; Liang, Yingjian; Zhang, Shugeng; Yin, Dalong; Wang, Jizhou; Pan, Shangha; Sun, Bo; Han, Jianyong; Sun, Jing; Lan, Yaliang; Wang, Yan; Liu, Xirui; Zhu, Mingxi; Cui, Yifeng; Zhang, Bo; Wu, Dehai; Liang, Shuhang; Liu, Yufeng; Song, Xuan; Lu, Zhao-Yang; Yang, Jingxuan; Li, Min; Liu, Lianxin

doi:10.1158/1078-0432.ccr-18-4113

Cited by 19 publications

(15 citation statements)

References 53 publications

(56 reference statements)

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“…OGDHL, as the main rate‐limiting component of 2‐oxoglutarate dehydrogenase complex (OGDHC) for glucose and glutamic acid degradation, plays an important role in the development of a wide variety of cancers 7 and tumors by influencing cell cycle arrest, 9 cell apoptosis, 8,15 and energy metabolism 10 . Studies have shown that methylation of the OGDHL promoter contributes to the development of many cancers such as breast cancer 11 and colon cancer 16 .…”

Section: Discussionmentioning

confidence: 99%

“…These activities increase the production of reactive oxygen species (ROS) and lead to cell apoptosis, which, in turn, can inhibit the proliferation and metastasis of cervical cancer cells 8 . A relevant study also showed that the miR‐214/ TWIST1 (microRNA 214/ Twist‐related protein 1) negative feedback loop mediated by OGDHL can inhibit the growth and metastasis of pancreatic cancer 9 . Shen et al demonstrated that in hepatocellular carcinoma (HCC), promoter hypermethylation and DNA copy deletion of OGDHL were associated with reduced OGDHL expression, and silencing of OGDHL can further lead to the occurrence and development of HCC by regulating the glutamine metabolism pathway 10 .…”

Section: Introductionmentioning

confidence: 99%

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OGDHL closely associates with tumor microenvironment and can serve as a prognostic biomarker for papillary thyroid cancer

et al. 2021

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Background Papillary thyroid cancer (PTC) is the most common type of thyroid cancer. However, due to the lack of reliable prognostic biomarkers for PTC, overtreatment has been on the rise. Therefore, our research aims to identify new and promising prognostic biomarkers and provide fresh perspectives for clinical decision making. Methods The RNA‐seq data and clinical data of PTC samples were obtained from The Cancer Genome Atlas data portal. GSE64912 and GSE83520 datasets were downloaded through the GEOquery R package. The difference in the expression of oxoglutarate dehydrogenase like ( OGDHL ) between PTC and normal tissues was explored by the Wilcoxon test. Kaplan–Meier (KM) and Cox regression analyses were used to further explore the prognostic value of OGDHL . The tumor microenvironments of PTC patients were explored based on ssGSEA and Tumor Immune Estimation Resource online database. Gene Set Enrichment Analysis (GSEA) was performed to explore the biological processes associated with OGDHL . Results The expression level of OGDHL in PTC was significantly altered compared to that in normal tissues ( p < 0.05). Various biological processes associated with OGDHL were also explored through GSEA. KM analysis suggested that the low‐ OGDHL group had a better overall survival [OS, p = 3.49e‐03, hazard ratio (HR) = 4.567]. The receiver operating characteristic curve also indicated the favorable prognostic potential of OGDHL . Moreover, OGDHL was proved to be an independent prognostic indicator in Cox analysis ( p = 1.33e‐02, HR = 0.152). In the analysis of the tumor microenvironment, the low‐ OGDHL group showed a lower immune score and stromal score, while tumor purity was higher. The expression of OGDHL was also closely correlated with the infiltration of immune cells. Conclusion Our study elucidated the influence of OGDHL on the prognosis of PTC and demonstrated its potential as a novel biomarker, which would provide new insights into the prognosis monitoring and clinical decision making in PTC patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

OGDHL closely associates with tumor microenvironment and can serve as a prognostic biomarker for papillary thyroid cancer

et al. 2021

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“…The supernatant was collected and completed the IP process following the protocol of A Dynabeads protein G IP kit (Thermofisher, US). The WB was performed as previously described [21]. MARC2 (#ab224097), p27 (#ab32034), CCND1 (#ab16663) and SKP2 (#ab183039) were purchased from Abcam; YAP (#14074S), HNF4A (#3113S), pRB (#9301T), pLATS1 (#9157), LATS1 (#9153), pYAP(127) (#13008) and pYAP (397) (#13619) were purchased from Cell Signaling Technology; RNF123 (#sc-101122) used for co-IP and RB (#sc-74562) was purchased from Santa [22,23].…”

Section: Co-immunoprecipitation (Co-ip) and Western Blot (Wb)mentioning

confidence: 99%

A novel mitochondrial amidoxime reducing component 2 is a favorable indicator of cancer and suppresses the progression of hepatocellular carcinoma by regulating the expression of p27

Wang

Yang

et al. 2020

Oncogene

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Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer-related mortality in the United States. Exploring the mechanism of HCC and identifying ideal targets is critical. In the present study, we demonstrated metabolism dysfunction might be a key diver for the development of HCC. The mitochondrial amidoxime reducing component 2 (MARC2) as a newly discovered molybdenum enzyme was downregulated in human HCC tissues and HCC cells. Downregulated MARC2 was significantly associated with clinicopathological characteristics of HCC, such as tumor size, AFP levels, and tumor grade and was an independent risk factor of poor prognosis. Both in vitro and in vivo studies suggested that MARC2 suppressed the progression of HCC by regulating the protein expression level of p27. The Hippo signaling pathway and RNF123 were required for this process. Moreover, MARC2 regulated expression of HNF4A via the Hippo signaling pathway. HNF4A was recruited to the promoter of MARC2 forming a feedback loop. MARC2 levels were downregulated by methylation. We demonstrated the prognostic value of MARC2 in HCC and determined the mechanism by which MARC2 suppressed the progression of HCC in this study. These findings may lead to new therapeutic targets for HCC.

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“…Ubiquitination is a multistep enzymatic process that results in the attachment of ubiquitin, or chains of ubiquitin, to the target protein. Previous studies have confirmed that ubiquitination is an important posttranslational modification and is involved in the regulation of a number of intracellular events, including transcription, the cell cycle, apoptosis, tumorigenesis and development [1][2][3][4]. The biochemical reaction of ubiquitination requires several essential enzymes, including E1, E2 and E3 enzymes.…”

Section: Introductionmentioning

confidence: 99%

“…The biochemical reaction of ubiquitination requires several essential enzymes, including E1, E2 and E3 enzymes. Among these enzymes, E3 ubiquitin ligases are regarded as receptors for recognizing specific target proteins [1][2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Role of the E3 Ubiquitin Ligase TRIM4 in Predicting the Prognosis of Hepatocellular Carcinoma

Dong¹,

Zhou²,

Sun³

et al. 2020

J. Cancer

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The E3 ubiquitin ligase TRIM4 has been reported to regulate the assembly of the antiviral signalling complex, induce mitochondrial aggregation and sensitize cells to H 2 O 2 -induced death. However, the relationship between TRIM4 and human malignancies, including hepatocellular carcinoma (HCC), is unclear. In this study, we detected the expression of TRIM4 in 134 pairs of HCC tissues and peritumoural tissues and investigated the association of TRIM4 expression with the prognosis of HCC. We found that the TRIM4 expression was much lower in HCC tissues than in peritumoural tissues and was significantly associated with vascular invasion, tumour capsule and Hong Kong Liver Cancer (HKLC) stage. Univariate and multivariate analyses revealed that the TRIM4 expression was an independent prognostic factor for overall survival (OS) and recurrence-free survival (RFS) in our HCC cohort. Patients with higher TRIM4 expression had a lower incidence of intrahepatic recurrence and a higher OS rate (p<0.001 and p<0.01, respectively). These results were further validated in another independent cohort of 200 HCC patients. In conclusion, the TRIM4 level in HCC tissues is an independent prognostic factor for HCC patients. Close clinical monitoring is recommended for patients with low TRIM4 expression.

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A Novel Oxoglutarate Dehydrogenase-Like Mediated miR-214/TWIST1 Negative Feedback Loop Inhibits Pancreatic Cancer Growth and Metastasis

Cited by 19 publications

References 53 publications

OGDHL closely associates with tumor microenvironment and can serve as a prognostic biomarker for papillary thyroid cancer

OGDHL closely associates with tumor microenvironment and can serve as a prognostic biomarker for papillary thyroid cancer

A novel mitochondrial amidoxime reducing component 2 is a favorable indicator of cancer and suppresses the progression of hepatocellular carcinoma by regulating the expression of p27

Role of the E3 Ubiquitin Ligase TRIM4 in Predicting the Prognosis of Hepatocellular Carcinoma

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