TNFAIP8 regulates autophagy, cell steatosis, and promotes hepatocellular carcinoma cell proliferation

Niture, Suryakant K.; Gyamfi, Maxwell Afari; Lin, Meixia; Chimeh, Uchechukwu; Dong, Xueyi; Zheng, Weifan; Moore, John T.; Kumar, Deepak

doi:10.1038/s41419-020-2369-4

Cited by 43 publications

(40 citation statements)

References 54 publications

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“…TNFAIP8 is known to regulate several genes associated with cell proliferation (IL-24, FAT3, LPHN2, EPHA3), fatty-acid oxidation (ACADL), and several oncogenes, for example, NFAT5, MALAT1, MET, FOXA1, KRAS, S100P, OSTF1 35 . TNFAIP8 has been shown to inhibit cell apoptosis and increase cell proliferation in numerous cancers including lung cancer [38][39][40][41] , liver cancer 42,43 , gastric cancer 44 , esophageal cancer (ESCC) 45,46 , pancreatic cancer 47 , and prostate cancer 32,34,35 . Here we extend the analysis of the oncogenic role of TNFAIP8 and investigate the role TNFAIP8 in skin cancer cell proliferation/survival and progression.…”

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confidence: 99%

RETRACTED ARTICLE: MicroRNA-205-5p inhibits skin cancer cell proliferation and increase drug sensitivity by targeting TNFAIP8

Niture

Lin

et al. 2021

Sci Rep

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Tumor necrosis factor-α-induced protein 8 (TNFAIP8) is a member of the TIPE/TNFAIP8 family which regulates tumor growth and survival. Our goal is to delineate the detailed oncogenic role of TNFAIP8 in skin cancer development and progression. Here we demonstrated that higher expression of TNFAIP8 is associated with basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma development in patient tissues. Induction of TNFAIP8 expression by TNFα or by ectopic expression of TNFAIP8 in SCC or melanoma cell lines resulted in increased cell growth/proliferation. Conversely, silencing of TNFAIP8 decreased cell survival/cell migration in skin cancer cells. We also showed that miR-205-5p targets the 3′UTR of TNFAIP8 and inhibits TNFAIP8 expression. Moreover, miR-205-5p downregulates TNFAIP8 mediated cellular autophagy, increased sensitivity towards the B-RAFV600E mutant kinase inhibitor vemurafenib, and induced cell apoptosis in melanoma cells. Collectively our data indicate that miR-205-5p acts as a tumor suppressor in skin cancer by targeting TNFAIP8.

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confidence: 99%

RETRACTED ARTICLE: MicroRNA-205-5p inhibits skin cancer cell proliferation and increase drug sensitivity by targeting TNFAIP8

Niture

Lin

et al. 2021

Sci Rep

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“…Activated mTORC1 inhibits autophagic cascade reaction by phosphorylating ATG13 and ULK1 to block the formation of pre-initiation complex [ 13 ], and by phosphorylating ATG14 to suppress the class III PI3K activity of ATG14-containing PIK3C3 [ 14 ]. mTORC1 integrates the upstream signaling of class I PI3K/AKT [ 15 ] and adenosine monophosphate kinase (AMPK) [ 16 ] (Fig. 2 ), which can sense the nutrient status and energy levels and deliver signaling to the key downstream 4EBP1 and p70S6K, which regulate protein translation.…”

Section: Mechanisms Of Autophagymentioning

confidence: 99%

Targeting autophagy to overcome drug resistance: further developments

2020

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Inhibiting cell survival and inducing cell death are the main approaches of tumor therapy. Autophagy plays an important role on intracellular metabolic homeostasis by eliminating dysfunctional or unnecessary proteins and damaged or aged cellular organelles to recycle their constituent metabolites that enable the maintenance of cell survival and genetic stability and even promotes the drug resistance, which severely limits the efficacy of chemotherapeutic drugs. Currently, targeting autophagy has a seemingly contradictory effect to suppress and promote tumor survival, which makes the effect of targeting autophagy on drug resistance more confusing and fuzzier. In the review, we summarize the regulation of autophagy by emerging ways, the action of targeting autophagy on drug resistance and some of the new therapeutic approaches to treat tumor drug resistance by interfering with autophagy-related pathways. The full-scale understanding of the tumor-associated signaling pathways and physiological functions of autophagy will hopefully open new possibilities for the treatment of tumor drug resistance and the improvement in clinical outcomes.

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“…Abnormal expression of several genes is critical in tumorigenesis and development of HCC. Recent research has shown that tumor necrosis factor-α-induced protein 8 (TNFAIP8) increases HCC cell survival by blocking apoptosis, promoting greater resistance to the anticancer drugs sorafenib and regorafenib ( Niture et al, 2020 ). High expression of ATP/GTP binding protein like 2 (AGBL2) is associated with significantly enhanced survival and proliferation of HCC cells in vitro and tumor growth in vivo ( Wang L. L. et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of Hub Genes Associated With Hepatocellular Carcinoma Using Robust Rank Aggregation Combined With Weighted Gene Co-expression Network Analysis

Song

Ding

et al. 2020

Front. Genet.

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Background Bioinformatics provides a valuable tool to explore the molecular mechanisms underlying pathogenesis of hepatocellular carcinoma (HCC). To improve prognosis of patients, identification of robust biomarkers associated with the pathogenic pathways of HCC remains an urgent research priority. Methods We employed the Robust Rank Aggregation method to integrate nine qualified HCC datasets from the Gene Expression Omnibus. A robust set of differentially expressed genes (DEGs) between tumor and normal tissue samples were screened. Weighted gene co-expression network analysis was applied to cluster DEGs and the key modules related to clinical traits identified. Based on network topology analysis, novel risk genes derived from key modules were mined and biological verification performed. The potential functions of these risk genes were further explored with the aid of miRNA–mRNA regulatory networks. Finally, the prognostic ability of these genes was assessed by constructing a clinical prediction model. Results Two key modules showed significant association with clinical traits. In combination with protein–protein interaction analysis, 29 hub genes were identified. Among these genes, 19 from one module showed a pattern of upregulation in HCC and were associated with the tumor node metastasis stage, and 10 from the other module displayed the opposite trend. Survival analyses indicated that all these genes were significantly related to patient prognosis. Based on the miRNA-mRNA regulatory network, 29 genes strongly linked to tumor activity were identified. Notably, five of the novel risk genes, ABAT, DAO, PCK2, SLC27A2, and HAO1, have rarely been reported in previous studies. Gene set enrichment analysis for each gene revealed regulatory roles in proliferation and prognosis of HCC. Least absolute shrinkage and selection operator regression analysis further validated DAO, PCK2, and HAO1 as prognostic factors in an external HCC dataset. Conclusion Analysis of multiple datasets combined with global network information presents a successful approach to uncover the complex biological mechanisms of HCC. More importantly, this novel integrated strategy facilitates identification of risk hub genes as candidate biomarkers for HCC, which could effectively guide clinical treatments.

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TNFAIP8 regulates autophagy, cell steatosis, and promotes hepatocellular carcinoma cell proliferation

Cited by 43 publications

References 54 publications

RETRACTED ARTICLE: MicroRNA-205-5p inhibits skin cancer cell proliferation and increase drug sensitivity by targeting TNFAIP8

RETRACTED ARTICLE: MicroRNA-205-5p inhibits skin cancer cell proliferation and increase drug sensitivity by targeting TNFAIP8

Targeting autophagy to overcome drug resistance: further developments

Identification of Hub Genes Associated With Hepatocellular Carcinoma Using Robust Rank Aggregation Combined With Weighted Gene Co-expression Network Analysis

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