Loss of tyrosine catabolic enzyme HPD promotes glutamine anaplerosis through mTOR signaling in liver cancer

Man Tong; Tin-Lok Wong; Hongzhi Zhao; Yuanyuan Zheng; Yu-Nong Xie; Cheuk-Hin Li; Lei Zhou; Noélia Che; Jing-Ping Yun; Kwan Man; Terence Kin-Wah Lee; Zongwei Cai; Stephanie Ma

doi:10.1016/j.celrep.2021.109976

Loss of tyrosine catabolic enzyme HPD promotes glutamine anaplerosis through mTOR signaling in liver cancer

Cell Reports ◽

10.1016/j.celrep.2021.109617 ◽

2021 ◽

Vol 36 (8) ◽

pp. 109617

Author(s):

Man Tong ◽

Tin-Lok Wong ◽

Hongzhi Zhao ◽

Yuanyuan Zheng ◽

Yu-Nong Xie ◽

...

Keyword(s):

Liver Cancer ◽

Mtor Signaling ◽

Catabolic Enzyme

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miR-125a inhibits the migration and invasion of liver cancer cells via suppression of the PI3K/AKT/mTOR signaling pathway

Oncology Letters ◽

10.3892/ol.2015.3264 ◽

2015 ◽

Vol 10 (2) ◽

pp. 681-686 ◽

Cited By ~ 41

Author(s):

HAO TANG ◽

RONG-PING LI ◽

PING LIANG ◽

YA-LONG ZHOU ◽

GUANG-WEI WANG

Keyword(s):

Liver Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Mtor Signaling ◽

Migration And Invasion ◽

Mtor Signaling Pathway ◽

Liver Cancer Cells

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Kaempferol inhibits proliferation, migration, and invasion of liver cancer HepG2 cells by down-regulation of microRNA-21

International Journal of Immunopathology and Pharmacology ◽

10.1177/2058738418814341 ◽

2018 ◽

Vol 32 ◽

pp. 205873841881434 ◽

Cited By ~ 14

Author(s):

Genglong Zhu ◽

Xialei Liu ◽

Haijing Li ◽

Yang Yan ◽

Xiaopeng Hong ◽

...

Keyword(s):

Cell Proliferation ◽

Liver Cancer ◽

Signaling Pathway ◽

Hepg2 Cell ◽

Cell Apoptosis ◽

Hepg2 Cells ◽

Mtor Signaling ◽

Brdu Incorporation ◽

Migration And Invasion ◽

Mtor Signaling Pathway

Liver cancer is one of the most common and lethal cancers in human digestive system, which kills more than half a million people every year worldwide. This study aimed to investigate the effects of kaempferol, a flavonoid compound isolated from vegetables and fruits, on hepatic cancer HepG2 cell proliferation, migration, invasion, and apoptosis, as well as microRNA-21 (miR-21) expression. Cell viability was detected using cell counting kit-8 (CCK-8) assay. Cell proliferation was measured using 5-bromo-2′-deoxyuridine (BrdU) incorporation assay. Cell apoptosis was assessed using Guava Nexin assay. Cell migration and invasion were determined using two-chamber migration (invasion) assay. Cell transfection was used to change the expression of miR-21. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to analyze the expressions of miR-21 and phosphatase and tensin homologue (PTEN). Expression of key proteins involved in proliferation, apoptosis, migration, invasion, and phosphatidylinositol 3-kinase/protein kinase 3/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway were evaluated using western blotting. Results showed that kaempferol significantly inhibited HepG2 cell proliferation, migration, and invasion, and induced cell apoptosis. Kaempferol remarkably reduce the expression of miR-21 in HepG2 cells. Overexpression of miR-21 obviously reversed the effects of kaempferol on HepG2 cell proliferation, migration, invasion, and apoptosis. Moreover, miR-21 negatively regulated the expression of PTEN in HepG2 cells. Kaempferol enhanced the expression of PTEN and inactivated PI3K/AKT/mTOR signaling pathway in HepG2 cells. In conclusion, kaempferol inhibited proliferation, migration, and invasion of HepG2 cells by down-regulating miR-21 and up-regulating PTEN, as well as inactivating PI3K/AKT/mTOR signaling pathway.

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NEIL3 contributes toward the carcinogenesis of liver cancer and regulates PI3K/Akt/mTOR signaling

Experimental and Therapeutic Medicine ◽

10.3892/etm.2021.10487 ◽

2021 ◽

Vol 22 (4) ◽

Author(s):

Weichen Wang ◽

Qing Yin ◽

Shanshan Guo ◽

Jun Wang

Keyword(s):

Liver Cancer ◽

Mtor Signaling

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Somatic mutation signatures in primary liver tumors of workers exposed to ionizing radiation

Scientific Reports ◽

10.1038/s41598-019-54773-z ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

David S. Goerlitz ◽

Jan Blancato ◽

Archana Ramesh ◽

Md. Islam ◽

Garrett T. Graham ◽

...

Keyword(s):

Liver Cancer ◽

Ionizing Radiation ◽

Chromatin Remodeling ◽

Liver Tumors ◽

Strand Break ◽

Mtor Signaling ◽

Driver Mutations ◽

Driver Genes ◽

Primary Liver Tumors ◽

Mutational Landscape

AbstractLiver cancer is associated with genetic mutations caused by environmental exposures, including occupational exposure to alpha radiation emitted by plutonium. We used whole exome sequencing (WES) to characterize somatic mutations in 3 histologically distinct primary liver tumors (angiosarcoma of the liver (ASL), cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC)) from Mayak worker subjects occupationally exposed to ionizing radiation (IR) to investigate the contribution of IR to the mutational landscape of liver cancer. DNA sequence analysis revealed these tumors harbor an excess of deletions, with a deletions:substitutions ratio similar to that previously reported in radiation-associated tumors. These tumors were also enriched for clustered mutations, a signature of radiation exposure. Multiple tumors displayed similarities in abrogated gene pathways including actin cytoskeletal signaling and DNA double-strand break (DSB) repair. WES identified novel candidate driver genes in ASL involved in angiogenesis and PIK3CA/AKT/mTOR signaling. We confirmed known driver genes of CCA, and identified candidate driver genes involved in chromatin remodeling. In HCC tumors we validated known driver genes, and identified novel putative driver genes involved in Wnt/β-catenin signaling, chromatin remodeling, PIK3CA/AKT/mTOR signaling, and angiogenesis. This pilot study identifies several novel candidate driver mutations that are likely to be caused by IR exposure, and provides the first data on the mutational landscape of liver cancer after IR exposure.

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