<scp>BCAT</scp>1, a key prognostic predictor of hepatocellular carcinoma, promotes cell proliferation and induces chemoresistance to cisplatin

Zheng, Yijing; Hu, Weixin; Chen, Bicheng; Grahn, Tan Hooi Min; Zhao, Yanrong; Bao, Hai-Li; Zhu, Yuan Xiao; Zhang, Qiyu

doi:10.1111/liv.13178

Cited by 77 publications

(71 citation statements)

References 14 publications

(15 reference statements)

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“…Our results confirm earlier studies reporting increased blood levels in these amino acids in CLD patients and subsequent decreased levels in HCC patients [63]. These metabolic shifts from CLD to HCC can be explained by an increased expression of branched-chain amino acid enzymes to enhance tumor proliferation and may reflect chemotherapy resistance [63][64][65]. Non-essential amino acids such as aspartate and proline have diverse functions in cancer metabolism, including as antioxidants in redox status metabolism but also as substrates for post-translational and epigenetic modifications [66].…”

Section: Discussionsupporting

confidence: 93%

“…Similarly, we found important differences in nitrogen metabolism, specifically branched-chain amino acids and non-essential amino acids. Our results confirm earlier studies reporting increased blood levels in these amino acids in CLD patients and subsequent decreased levels in HCC patients [63]. These metabolic shifts from CLD to HCC can be explained by an increased expression of branched-chain amino acid enzymes to enhance tumor proliferation and may reflect chemotherapy resistance [63][64][65].…”

Section: Discussionsupporting

confidence: 91%

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Sugar Alcohols Have a Key Role in Pathogenesis of Chronic Liver Disease and Hepatocellular Carcinoma in Whole Blood and Liver Tissues

Ismail

Fiehn

Elfert

et al. 2020

Cancers

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The major risk factors for hepatocellular carcinoma (HCC) are hepatitis C and B viral infections that proceed to Chronic Liver Disease (CLD). Yet, the early diagnosis and treatment of HCC are challenging because the pathogenesis of HCC is not fully defined. To better understand the onset and development of HCC, untargeted GC-TOF MS metabolomics data were acquired from resected human HCC tissues and their paired non-tumor hepatic tissues (n = 46). Blood samples of the same HCC subjects (n = 23) were compared to CLD (n = 15) and healthy control (n = 15) blood samples. The participants were recruited from the National Liver Institute in Egypt. The GC-TOF MS data yielded 194 structurally annotated compounds. The most strikingly significant alteration was found for the class of sugar alcohols that were up-regulated in blood of HCC patients compared to CLD subjects (p < 2.4 × 10−12) and CLD compared to healthy controls (p = 4.1 × 10−7). In HCC tissues, sugar alcohols were the most significant (p < 1 × 10−6) class differentiating resected HCC tissues from non-malignant hepatic tissues for all HCC patients. Alteration of sugar alcohol levels in liver tissues also defined early-stage HCC from their paired non-malignant hepatic tissues (p = 2.7 × 10−6). In blood, sugar alcohols differentiated HCC from CLD subjects with an ROC-curve of 0.875 compared to 0.685 for the classic HCC biomarker alpha-fetoprotein. Blood sugar alcohol levels steadily increased from healthy controls to CLD to early stages of HCC and finally, to late-stage HCC patients. The increase in sugar alcohol levels indicates a role of aldo-keto reductases in the pathogenesis of HCC, possibly opening novel diagnostic and therapeutic options after in-depth validation.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

Sugar Alcohols Have a Key Role in Pathogenesis of Chronic Liver Disease and Hepatocellular Carcinoma in Whole Blood and Liver Tissues

Ismail

Fiehn

Elfert

et al. 2020

Cancers

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“…29 BCAT1 indicated poor prognosis and led to cell proliferation and chemoresistance in hepatocellular carcinoma. 30 BCAT1 could be activated by c-Myc, and overexpression of BCAT1 induces cell proliferation, migration and invasion in nasopharyngeal carcinoma. 31 In total, BCAT1 may be a pivotal oncogene in human malignancies, including glioma.…”

Section: Discussionmentioning

confidence: 98%

<p>LINC00963 Confers Oncogenic Properties in Glioma by Regulating the miR-506/BCAT1 Axis</p>

Ye¹,

Xu²,

Ge³

et al. 2020

CMAR

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Background: Glioma is a prevalent disease of the central nervous system with a high incidence and mortality rate. Many long noncoding RNAs (lncRNAs) have been determined to be critical regulators of glioma oncogenesis. However, the function and mechanism of LINC00963 in glioma have not been fully elucidated. Methods: The expression level of RNA was determined by qRT-PCR, and the protein level was determined by Western blot analysis. A luciferase activity assay was conducted to verify the interaction between miRNA and lncRNA or the target gene. The proliferation, cell cycle distribution, invasion, and migration were evaluated by MTT, EdU, flow cytometry, woundhealing and Transwell invasion assays, respectively. In vivo tumor growth was evaluated in a xenograft nude mouse model. Results: We found that LINC00963 was upregulated in glioma cells and tissues and associated with the poor prognosis of patients with glioma. Ectopic expression of LINC00963 promoted cell proliferation, cell cycle progression, migration, and invasion in vitro and tumorigenesis in vivo. Mechanistically, the results of luciferase activity and RNA pulldown assays validated that LINC00963 could act as a molecular sponge of miR-506. Reciprocal repression was found between LINC00963 and miR-506. In addition, BCAT1 was identified as a target of miR-506, and both the mRNA and protein levels of BCAT1 were reduced by miR-506. In tumor tissues, the expression of BCAT1 was negatively and positively correlated with miR-506 and LINC00963 expression, respectively. The reintroduction of BCAT1 in glioma cells abolished the tumor suppressive function of miR-506 by promoting cell viability and motility. The upregulated LINC00963 and BCAT1 were associated with the aggressive phenotypes of tumors. Conclusion: Our data revealed that LINC00963 confers oncogenic function in the progression of glioma and that the LINC00963/miR-506/BCAT1 axis may be a novel mechanism and therapeutic strategy for this disease.

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“…101,102 Studies showed that BCAT1 is a downstream target to MYC oncogene. [103][104][105] The aberrant expression of BCAT1 is linked to enhanced proliferation of several types of cancer cells 103,[106][107][108] and poor prognosis in HCC patients. 102 main benefits.…”

Section: Targeting Hematopoietic Progenitor Kinase 1 (Hpk-1)mentioning

confidence: 99%

Revolutionizing the landscape of colorectal cancer treatment: The potential role of immune checkpoint inhibitors

Tolba

2020

Intl Journal of Cancer

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Colorectal cancer (CRC) represents the third cause of cancer-related mortalities worldwide. The progression of CRC to the metastatic phase significantly compromises the overall survival rates. Despite the advances in the therapeutic protocols, CRC treatment is still challenging. Cancer immunotherapy joined the ranks of surgery, chemotherapy, radiotherapy and targeted therapy as the fifth pillar in the foundation of cancer therapeutics. Interruption of the immunosuppressive signals within the tumor microenvironment and reactivation of antitumor immunity via targeting the molecular immune checkpoints generated promising therapeutic outcomes in several types of hard-to-treat cancers. The year 2017 witnessed the first US Food and Drug Administration (FDA) approval of immune checkpoint inhibitor (ICI) immunotherapy for the management of CRC. The approval was granted to pembrolizumab (anti-PD-1) for the treatment of patients with advanced/metastatic solid malignancies with mismatch-repair deficiency including CRCs. Such natively immunogenic tumors constitute only a minor percentage of all CRCs. Therefore, it is imperative to utilize novel combinatorial regimens to enhance the response of a wider range of CRC tumors to cancer immunotherapy and help in extending the survival rates in patients with advanced/metastatic disease. This review highlights the novel approaches under clinical development to overcome the resistance of CRCs to immunotherapy and improve the therapeutic outcomes. K E Y W O R D S clinical trials, colon cancer, immune checkpoint inhibitors, immunotherapy 1 | INTRODUCTION Colorectal cancer (CRC) is ranked as the third cause of cancer death worldwide. 1 The progression to the metastatic stage cuts down the overall survival rate to 10%. 2 Advances in treatment options for the metastatic stage of the disease only extended the median overall survival from 18 to 30 months. 2,3 Therefore, it is imperative to find better therapeutic strategies for patients with advanced/metastatic CRC. Cancer Immunotherapy is considered the fifth pillar for cancer therapy that proved effectiveness in the management of several types of hard-to-treat cancers. 4,5 Clinical testing of programmed cell death receptor (PD)-1 mAb in patients with metastatic CRC demonstrated promising outcomes with progression-free survival rates of 78% and 11% in mismatch-repair-deficient (dMMR) vs mismatch-repairproficient (pMMR) tumors. 6,7 It is noteworthy that dMMR or microsatellite unstable (MSI) CRC tumors represent only a small percentage

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BCAT1, a key prognostic predictor of hepatocellular carcinoma, promotes cell proliferation and induces chemoresistance to cisplatin

Abstract: BCAT1 plays a pathogenic role in HCC by causing cell proliferation and chemoresistance. The MYC transcription factor is involved in regulating the transcriptional activity of BCAT1. BCAT1 expression has prognostic significance for the survival of patients with HCC.

Cited by 77 publications

References 14 publications

Sugar Alcohols Have a Key Role in Pathogenesis of Chronic Liver Disease and Hepatocellular Carcinoma in Whole Blood and Liver Tissues

Sugar Alcohols Have a Key Role in Pathogenesis of Chronic Liver Disease and Hepatocellular Carcinoma in Whole Blood and Liver Tissues

<p>LINC00963 Confers Oncogenic Properties in Glioma by Regulating the miR-506/BCAT1 Axis</p>

Revolutionizing the landscape of colorectal cancer treatment: The potential role of immune checkpoint inhibitors

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