<i>P57</i>‐mediated autophagy promotes the efficacy of <i>EGFR</i> inhibitors in hepatocellular carcinoma

Li, Wenyuan; Li, Qing; Li, Jing; Wu, Tao; Han, Lili; Wang, Yu; Yu, Sizhe; Kang, Nan; Guo, Hui

doi:10.1111/liv.13957

Cited by 16 publications

(12 citation statements)

References 28 publications

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“…36 Specifically, an enhancement in the extent of PI3K, Akt, and mTOR phosphorylation was reported to be involved in the decline of LC3B-II in HCC. 37 However, in this study, the potential association between LINC01419 and the PI3K/Akt/mTOR signaling pathway requires further exploration, verifying specific molecular targets verified by more experiments, such as RNA immunoprecipitation (RIP), cross-linking immunoprecipitation (CLIP), chromatin immunoprecipitation (CHIP), and fluorescence in situ hybridization (FISH).…”

Section: R E T R a C T E Dmentioning

confidence: 87%

RETRACTED: Downregulation of long noncoding RNA LINC01419 inhibits cell migration, invasion, and tumor growth and promotes autophagy via inactivation of the PI3K/Akt1/mTOR pathway in gastric cancer

2019

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Background: Accumulating evidence has highlighted the crucial role of long noncoding RNAs (lncRNAs) in the tumorigenesis of gastric cancer (GC), which is the most common gastrointestinal malignancy. The present study aimed to identify the capacity of lncRNA LINC01419 (LINC01419) in GC progression, with the potential mechanism explored. Methods: Highly expressed lncRNAs were identified by in silico analysis, with the LINC01419 expression in GC tissues measured using reverse transcription-quantitative PCR (RT-qPCR). The GC cells were subsequently transfected with siRNA against LINC01419 or Rapamycin (the inhibitor of the mTOR pathway), or both, in order to measure cell migration and invasion in vitro as well as tumor growth and metastasis in vivo. Moreover, the expression of PI3K/Akt1/mTOR pathway-associated factors was determined. Results: LINC01419, highly expressed in GC samples of the Gene Expression Omnibus database, was observed to be markedly upregulated in GC tissues. Moreover, LINC01419 silencing, or PI3K/Akt1/mTOR pathway inhibition, exhibited an inhibitory role in GC cell migration and invasion in vitro, coupled with promoted cell autophagy in vitro, and inhibited tumor growth and metastasis in vivo. It was also revealed that LINC01419 silencing blocked the PI3K/Akt1/mTOR pathway, as proved by decreased extents of Akt1 and mTOR phosphorylation. Conclusions: In conclusion, LINC01419 inhibition may suppress GC cell invasion and migration, and promote autophagy via inhibition of the PI3K/Akt1/mTOR pathway. This provides significant theoretical basis and possibilities for further elucidation of the molecular mechanism of GC and finding new molecular-targeted therapeutic regimens.

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Section: R E T R a C T E Dmentioning

confidence: 87%

RETRACTED: Downregulation of long noncoding RNA LINC01419 inhibits cell migration, invasion, and tumor growth and promotes autophagy via inactivation of the PI3K/Akt1/mTOR pathway in gastric cancer

2019

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“…EGFR is an important factor in HCC and previous studies have demonstrated that EGFR is involved in various HCC mechanisms including cell proliferation, latestage metastasis, treatment and drug resistance. [30][31][32][33][34][35] However, anti-EGFR agencies do not show ideal results in HCC involving extremely complicated pathways. 10,12 Lin et al reported that the anti-EGFR drug resistance in HCC is caused by the promoted interaction of EGFR with mTORC2.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic Analysis of Hepatocellular Carcinoma Cell Lines to the Efficacy of Nimotuzumab

Wang¹,

Zhang

Gong

et al. 2021

IJGM

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Introduction Hepatocellular carcinoma (HCC) continues to be a cancer with rising incidence, high mortality, and recurrence rate. The therapeutic effects on HCC are not satisfactory currently. Epidermal growth factor receptor (EGFR) is an important factor, while anti-EGFR agencies have not shown ideal results in HCC. Materials and Methods We tested efficacy of nimotuzumab and EGFR expression on cell surface in six HCC cell lines (Hep 3B2.1–7, Li-7, PLC/PRF/5, SK-HEP-1, SNU-182, and SNU-387). Then, we analyzed RNA sequences of every cell line and performed a bioinformatic analysis. Differentially expressed genes (DEGs) were analyzed. The data, TCGA-LIHC from The Cancer Genome Atlas (TCGA) and GSE102079 from Gene Expression Omnibus (GEO), were used to analyse DEGs of Hoshida subclass. Results Hep 3B2.1–7 and PLC/PRF/5 were sensitive to nimotuzumab whereas Li-7, SK-HEP-1, SNU-182, and SNU-387 cell lines were resistant. Then, we compared the DEGs between sensitive and resistant group cell lines. We enriched DEGs in GO and KEGG and performed GSEA in each group. Genes in two groups did not show obvious different expressions in EGFR pathways, while Hoshida subclass of HCC seemed to associate with the efficacy of nimotuzumab in that S2 and S3 showed better therapeutic effect than S1. Therefore, we analyzed genes in human tumor samples which were from TCGA-LIHC and GSE102079. We found that COL1A1, COL1A2, COL3A1, and MMP9 were the focus DEGs of S1 and S2 & S3 related to EGFR. Conclusion The efficacy of nimotuzumab in HCC did not show direct relevance with EGFR protein expression and EGFR-related pathway. However, efficacy could associate with Hoshida subclass of HCC. Three ECM genes (COL1A1, COL1A2, COL3A1) and MMP9 were paid attention, as they might play important roles in the curative effect of nimotuzumab in HCC.

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“…The P57-mediated autophagy promotes the efficacy of EGFR [epidermal growth factor receptor] inhibitors. Upregulation of p57 decreases the level of autophagy and enhances the decrease in cell viability in hepatocellular carcinoma [40]. In addition, p57 expression makes cancer cells more sensitive to cisplatin.…”

Section: Cis-cet Me L-cis-cetmentioning

confidence: 99%

Melatonin, p21, p27, p53, p57, MDM2 ve KRAS Genlerinin modülasyonu yoluyla Pankreas Karsinomu Hücrelerinin (PANC-1) Cisplatin ve Cetuximab'a Kemosensitivitesini Artırır

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Özkanlar

2021

Türk Doğa Ve Fen Dergisi

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In the present study, the effects on cell viability and some oncogenes and tumor suppressor genes were investigated after melatonin, cetuximab, and cisplatin were administered alone or in combination to the pancreatic ductal adenocarcinoma cell line (PANC-1). The cells were left for 48 h incubation after applying drugs on the PANC-1 cells. The metabolic effects of the substances on cell viability at the end of incubation were measured by MTT analysis. The gene expressions of p21, p27, p53, p57, MDM2, and KRAS were determined by RT-PCR. The use of melatonin combined with cisplatin or cetuximab increased p21 and p57 genes and decreased the KRAS gene. Furthermore, melatonin combined with cetuximab increased p27 gene expression and decreased cell viability compared to cetuximab alone. The cell viability was the lowest in cisplatin and cisplatin plus melatonin and/or cetuximab groups. The p53 were highest in the cisplatin groups while cisplatin plus melatonin decreased the p53 gene and its autoregulator MDM2 gene compared to cisplatin alone. In conclusion, melatonin in combination with cisplatin and cetuximab enhances the tumor suppressor genes p21, p27, and p57 along with a modulation of the oncogenic gene KRAS suggesting the potential of melatonin as a therapeutic approach in combination therapy of pancreatic ductal adenocarcinoma.

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P57‐mediated autophagy promotes the efficacy of EGFR inhibitors in hepatocellular carcinoma

Cited by 16 publications

References 28 publications

RETRACTED: Downregulation of long noncoding RNA LINC01419 inhibits cell migration, invasion, and tumor growth and promotes autophagy via inactivation of the PI3K/Akt1/mTOR pathway in gastric cancer

RETRACTED: Downregulation of long noncoding RNA LINC01419 inhibits cell migration, invasion, and tumor growth and promotes autophagy via inactivation of the PI3K/Akt1/mTOR pathway in gastric cancer

Bioinformatic Analysis of Hepatocellular Carcinoma Cell Lines to the Efficacy of Nimotuzumab

Melatonin, p21, p27, p53, p57, MDM2 ve KRAS Genlerinin modülasyonu yoluyla Pankreas Karsinomu Hücrelerinin (PANC-1) Cisplatin ve Cetuximab'a Kemosensitivitesini Artırır

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