LncRNA H19 downregulation confers erlotinib resistance through upregulation of PKM2 and phosphorylation of AKT in EGFR-mutant lung cancers

Chen, Chen; Liu, Wei-Ran; Zhang, Bin; Zhang, Lian-Min; Li, Chenguang; Liu, Chang; Zhang, Hua; Huo, Yansong; Ma, Yiming; Tian, Pengfei; Qi, Qi; Li, Jingjing; Tang, Zhe; Zhang, Zhen Fa; Giaccone, G.; Yue, Dongsheng; Wang, Changli

doi:10.1016/j.canlet.2020.05.009

Cited by 64 publications

(47 citation statements)

References 44 publications

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“…There are activating mutations located in the tyrosine kinase domain of the EGFR gene, including a 19-exon deletion and a point mutation in the 21 exon L858R ( 31 – 33 ). These activating mutations make EGFR highly sensitive to EGFR-TKIs molecular targeted drugs, such as gefitinib and erlotinib, but patients also develop resistance to these drugs ( 34 – 36 ). Previous studies have shown that changes in lipid metabolism in cancer cells are associated with EGFR-TKI resistance ( 37 – 39 ), and the inhibition of intracellular lipid droplet synthesis can reverse the resistance of cancer cells to gefitinib ( 40 ).…”

Section: Introductionmentioning

confidence: 99%

Implications of lipid droplets in lung cancer: Associations with drug resistance (Review)

Jin

Yuan

2020

Oncol Lett

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Cancer cells usually show different metabolic patterns compared with healthy cells due to the reprogramming of metabolic processes. The process of lipid metabolism undergoes notable changes, leading to the accumulation of lipid droplets in cells. Additionally, this phenotype is considered an important marker of cancer cells. Lipid droplets are a highly dynamic type of organelle in the cell, which is composed of a neutral lipid core, a monolayer phospholipid membrane and lipid droplet-related proteins. Lipid droplets are involved in several biological processes, including cell proliferation, apoptosis, lipid metabolism, stress, immunity, signal transduction and protein trafficking. Epidermal growth factor receptor (EGFR)-activating mutations are currently the most effective therapeutic targets for non-small cell lung cancer. Several EGFR tyrosine kinase inhibitors (EGFR-TKIs) that target these mutations, including gefitinib, erlotinib, afatinib and osimertinib, have been widely used clinically. However, the development of acquired resistance has a major impact on the efficacy of these drugs. A number of previous studies have reported that the expression of lipid droplets in the tumor tissues of patients with lung cancer are elevated, whereas the association between elevated numbers of lipid droplets and drug resistance has received little attention. The present review describes the potential association between lipid droplets and drug resistance. Furthermore, the mechanisms and implications of lipid droplet accumulation in cancer cells are analyzed, as wells as the mechanism by which lipid droplets suppress endoplasmic reticulum stress and apoptosis, which are essential for the development and treatment of lung cancer. Contents

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Section: Introductionmentioning

confidence: 99%

Implications of lipid droplets in lung cancer: Associations with drug resistance (Review)

Jin

Yuan

2020

Oncol Lett

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“…However, some of responders relapsed because of acquired resistance. Recent studies showed that combination of EGFR tyrosine kinase inhibitor and AKT inhibitors could be a rational therapeutic approach for lung cancer patients [27]. Therefore, PI3K-Akt signaling pathway and EGFR tyrosine kinase inhibitor resistance pathways can be considered as the significant pathways of ginger for treating colon cancer.…”

Section: Discussionmentioning

confidence: 99%

Identification of the active substances and mechanisms of ginger for the treatment of colon cancer based on network pharmacology and molecular docking

et al. 2021

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Background and objective Colon cancer is occurring at an increasing rate and ginger (Zingiber officinale), as a commonly used herbal medicine, has been suggested as a potential agent for colon cancer. This study was aimed to identify the bioactive components and potential mechanisms of ginger for colon cancer prevention by an integrated network pharmacology approach. Methods The putative ingredients of ginger and its related targets were discerned from the TCMSP and Swiss target prediction database. After that, the targets interacting with colon cancer were collected using Genecards, OMIM, and Drugbank databases. KEGG pathway and GO enrichment analysis were performed to explore the signaling pathways related to ginger for colon cancer treatments. The PPI and compound-target-disease networks were constructed using Cytoscape 3.8.1. Finally, Discovery studio software was employed to confirm the key genes and active components from ginger. Results Six potential active compounds, 285 interacting targets in addition to 1356 disease-related targets were collected, of which 118 intersection targets were obtained. A total of 34 key targets including PIK3CA, SRC, and TP53 were identified through PPI network analysis. These targets were mainly focused on the biological processes of phosphatidylinositol 3-kinase signaling, cellular response to oxidative stress, and cellular response to peptide hormone stimulus. The KEGG enrichment manifested that three signaling pathways were closely related to colon cancer prevention of ginger, cancer, endocrine resistance, and hepatitis B pathways. TP53, HSP90AA1, and JAK2 were viewed as the most important genes, which were validated by molecular docking simulation. Conclusion This study demonstrated that ginger produced preventive effects against colon cancer by regulating multi-targets and multi-pathways with multi-components. And, the combined data provide novel insight for ginger compounds developed as new drug for anti-colon cancer.

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“…Cells (3000/well) were cultured for 48 h in 96-well plates. Followed by incubating with 10 μL CCK8 for 3-4 h, the absorbance was assessed using GloMax<sp>® System (Promega, WI, USA) at 450 nm ( 21 ).…”

Section: Methodsmentioning

confidence: 99%

LncRNA DLEU1 Contributes to the Growth and Invasion of Colorectal Cancer via Targeting miR-320b/PRPS1

Yang

Fan

et al. 2021

Front. Oncol.

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Growing evidences suggest that long non-coding RNAs (lncRNAs) are closely correlated to the development of human cancer, such as colorectal cancer (CRC). A previous report suggested that DLEU1 accelerated CRC development. However, DLEU1’s underlying mechanism in CRC remains unclear. In our study, the level of DLEU1 in CRC tissues is investigated by qRT-PCR. Our data exhibited that DLEU1 level was observably increased in CRC tissues and CRC cell lines and was closely associated with bad prognosis of CRC patients. CRC cell proliferation was repressed by sh-LncRNA DLEU1, whereas cell apoptosis was markedly stimulated. Moreover, knockdown of DLEU1 inhibited cell migration and invasion. Mechanistically, through interacting with miR-320b in CRC, DLEU1 promoted the level of PRPS1 which was a target of miR-320b. The rescue experiment confirmed that knockdown of DLEU1 repressed cell proliferation, migration and invasion while stimulated cell apoptosis via miR-320b/phosphoribosyl pyrophosphate synthetase 1 (PRPS1) axis. Meanwhile, the data of xenograft model exhibited that inhibition of DLEU1 suppressed tumor growth in vivo. In summary, DLEU1 knockdown may repress PRPS1 expression via miR-320b, and then repress cell proliferation, migration and invasion while stimulate cell apoptosis. Our research may provide a novel target for the treatment of CRC.

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LncRNA H19 downregulation confers erlotinib resistance through upregulation of PKM2 and phosphorylation of AKT in EGFR-mutant lung cancers

Cited by 64 publications

References 44 publications

Implications of lipid droplets in lung cancer: Associations with drug resistance (Review)

Implications of lipid droplets in lung cancer: Associations with drug resistance (Review)

Identification of the active substances and mechanisms of ginger for the treatment of colon cancer based on network pharmacology and molecular docking

LncRNA DLEU1 Contributes to the Growth and Invasion of Colorectal Cancer via Targeting miR-320b/PRPS1

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