Combination of ULK1 and LC3B improve prognosis assessment of hepatocellular carcinoma

Wu, Dong-hao; Wang, Tiantian; Ruan, Dan‐Yun; Li, Xing; Chen, Zhan-Hong; Wen, Ji; Q, Lin; Ma, Xiaokun; Wu, Xiang‐Yuan; Jia, Changchang

doi:10.1016/j.biopha.2017.10.025

Cited by 37 publications

(27 citation statements)

References 29 publications

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“…Zhao et al (2017) have found that beclin1 and LC3 can be potential prognostic markers in retrospective studies of ovarian cancer. Wu et al (2018) have demonstrated that ULK1 combined with LC3B would improve prognosis assessment of the HCC patients and so on. Thus, LC3 can also be combined with other related genes for clinical diagnosis.…”

Section: Studymentioning

confidence: 99%

Role of the autophagy-related marker LC3 expression in hepatocellular carcinoma: a meta-analysis

Meng

Lou

Yang

et al. 2020

J Cancer Res Clin Oncol

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Background Microtubule-associated protein 1 light chain 3 (LC3), an autophagic gene, has been reported as a vital marker for many diseases and cancers. However, the role of LC3 in hepatocellular carcinoma (HCC) was not still investigated. Therefore, we conducted a meta-analysis to examine the association of LC3 with its clinicopathological and prognostic in HCC. Methods We consulted the PubMed, Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure and Wan Fang databases for published studies on LC3 in HCC. Newcastle-Ottawa scale was used to screen the quality of the literature. The statistical analysis was calculated by STATA 14.2. Results Of the 1329 titles identified, 10 articles involving 949 patients in HCC were included in this meta-analysis. The results of our study show that increased LC3 expression is related to size of tumor, but not to gender, age, number of tumor, liver cirrhosis, HBsAg, TNM stage, alpha fetoprotein, vascular invasion and histological grade. Positive LC3 expression was associated with overall survival by pooled hazard ratio. Conclusions This meta-analysis indicated that positive LC3 expression was related to size of tumor, and could predict prognosis in human hepatocellular carcinoma.

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Section: Studymentioning

confidence: 99%

Role of the autophagy-related marker LC3 expression in hepatocellular carcinoma: a meta-analysis

Meng

Lou

Yang

et al. 2020

J Cancer Res Clin Oncol

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“…The framework here applied could be extended more broadly to other targets to help in the classification of mutational effects in disease, to prioritize variants for experimental validation or select the appropriate biological readouts for experiments.suggested to play essential scaffolding roles for autophagosome formation and maturation [9]. ULK1 has been reported overexpressed or downregulated in different cancer types or subtypes [25][26][27][28]. Autophagy in general has a strong association with cancer and can act with a dual role in a context-dependent way, being both tumor suppressor or promoter [29,30].…”

mentioning

confidence: 99%

A Pan-Cancer assessment of alterations of the kinase domain of ULK1, an upstream regulator of autophagy

Kumar

Papaleo

2019

Preprint

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Autophagy is a key clearance process for the cell to recycle damaged cellular components. Autophagy is also well known for its dual role in cancer, acting as both tumor suppressor or promoter in a context-dependent way. One important upstream regulator of autophagy is the kinase ULK1. Several structures of the kinase domain of ULK1 have been solved, but a comprehensive study, including molecular dynamics, is currently missing. Also, an exhaustive description of the landscape of ULK1 cancer-related alterations is presently lacking. We here exploited the large amount of data on more than 30 cancer types through The Cancer Genome Atlas and the Recount2 initiatives to identify and analyze the atlas of ULK1 alterations in terms of gene expression and mutations. Moreover, we predicted the effects of mutations on ULK1 function and structural stability using a computational workflow accounting for protein dynamics and different layers of changes that a mutation can induce in a protein.We discovered that ULK1, along with ULK2 are down-regulated in gynecological tumors, suggesting an impairment of the upstream regulation of autophagy. In other cancer types, ULK2 can compensate for ULK1 downregulation and, in the majority of the cases, no marked changes in expression level have been found for both genes. We identified 36 missense mutations of ULK1 especially in uterine, colon, stomach and lung cancer that were co-occurring with mutations in a large number of ULK1 interactors, suggesting a pronounced effect of the upstream steps of autophagy in these cancer types. Moreover, our study allowed to pinpoint that more than 50% of the mutations of ULK1 found in the cancer samples affect protein stability, which is likely to affect the cellular level and turnover of the protein. Among the damaging mutations for stability, A125T, F273V, L215P, F14L, and G12D are also predicted not to alter the functional state of the protein. Three mutations (S184F, D102N, and A28V) are predicted with the only impact on kinase activity, either modifying the functional dynamics of the protein or the capability to exert effects from distal site to the functional and catalytic regions. The framework here applied could be extended more broadly to other targets to help in the classification of mutational effects in disease, to prioritize variants for experimental validation or select the appropriate biological readouts for experiments.suggested to play essential scaffolding roles for autophagosome formation and maturation [9]. ULK1 has been reported overexpressed or downregulated in different cancer types or subtypes [25][26][27][28]. Autophagy in general has a strong association with cancer and can act with a dual role in a context-dependent way, being both tumor suppressor or promoter [29,30]. AMPK-ULK1 mediated autophagy also induces resistance against bromodomain and extraterminal domain inhibitors, which are novel epigenetic therapeutics for acute myeloid leukemia [31].So it can be a pivotal target to curb the chemotherapeutic resistance in cancers....

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“…However, enough evidence showed that sorafenib is able to promote autophagy-mediated cell death by overexpression of autophagy markers, including Beclin-1, by induction of ER stress and by suppression of the autophagy inhibitor mTORC1 and Akt [118]. Another study showed that the analysis and comparison of combined autophagy biomarkers, such as ULK1 and LC3B, with patient prognosis would better represent the complex stage of autophagy [119]. Wu et al [120] showed that high LC3B expression is a novel prognostic biomarker in HCC patients, which was associated with vascular invasion and lymph node metastasis.…”

Section: Molecular Mechanisms and Biomarkers Of Autophagymentioning

confidence: 99%

Autophagy: A Potential Therapeutic Target of Polyphenols in Hepatocellular Carcinoma

Kiruthiga

Devi

Nabavi

et al. 2020

Cancers

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Autophagy is a conserved biological phenomenon that maintains cellular homeostasis through the clearing of damaged cellular components under cellular stress and offers the cell building blocks for cellular survival. Aberrations in autophagy subsidize to various human pathologies, such as dementia, cardiovascular diseases, leishmaniosis, influenza, hepatic diseases, and cancer, including hepatocellular carcinoma (HCC). HCC is the fifth common mortal type of liver cancer globally, with an inhomogeneous topographical distribution and highest incidence tripled in men than women. Existing treatment procedures with liver cancer patients result in variable success rates and poor prognosis due to their drug resistance and toxicity. One of the pathophysiological mechanisms that are targeted during the development of anti-liver cancer drugs is autophagy. Generally, overactivated autophagy may lead to a non-apoptotic form of programmed cell death (PCD) or autophagic cell death or type II PCD. Emerging evidence suggests that manipulation of autophagy could induce type II PCD in cancer cells, acting as a potential tumor suppressor. Hence, altering autophagic signaling offers new hope for the development of novel drugs for the therapy of resistant cancer cells. Natural polyphenolic compounds, including flavonoids and non-flavonoids, execute their anticarcinogenic mechanism through upregulating tumor suppressors and autophagy by modulating canonical (Beclin-1-dependent) and non-canonical (Beclin-1-independent) signaling pathways. Additionally, there is evidence signifying that plant polyphenols target angiogenesis and metastasis in HCC via interference with multiple intracellular signals and decrease the risk against HCC. The current review offers a comprehensive understanding of how natural polyphenolic compounds exhibit their anti-HCC effects through regulation of autophagy, the non-apoptotic mode of cell death.

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Combination of ULK1 and LC3B improve prognosis assessment of hepatocellular carcinoma

Cited by 37 publications

References 29 publications

Role of the autophagy-related marker LC3 expression in hepatocellular carcinoma: a meta-analysis

Role of the autophagy-related marker LC3 expression in hepatocellular carcinoma: a meta-analysis

A Pan-Cancer assessment of alterations of the kinase domain of ULK1, an upstream regulator of autophagy

Autophagy: A Potential Therapeutic Target of Polyphenols in Hepatocellular Carcinoma

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