LncRNA MILIP links YBX1 to translational activation of Snai1 and promotes metastasis in clear cell renal cell carcinoma

Combination therapy as an important treatment option for lung cancer has been attracting attention due to the primary and acquired resistance of chemotherapeutic drugs in the clinical application. In the present study, as a new therapy strategy, concomitant treatment with time-restricted feeding (TRF) plus cisplatin (DDP) on lung cancer growth was investigated in DDP-resistant and DDP-sensitive lung cancer cells. We first found that TRF significantly enhanced the drug susceptibility of DDP in DDP-resistant A549 (A549/DDP) cell line, illustrated by reversing the inhibitory concentration 50 (IC50) values of A549/DDP cells to normal level of parental A549 cells. We also found that TRF markedly enhanced DDP inhibition on cell proliferation, migration, as well as promoted apoptosis compared to the DDP alone group in A549, H460 and A549/DDP cells lines. We further revealed that the synergistic anti-tumor effect of combined DDP and TRF was greater than that of combined DDP and simulated fasting condition (STS), a known anti-tumor cellular medium. Moreover, mRNA sequence analysis from A549/DDP cell line demonstrated the synergistic anti-tumor effect involved in upregulated pathways in p53 signaling pathway and apoptosis. Notably, compared with the DDP alone group, combination of TRF and DDP robustly upregulated the P53 protein expression without mRNA level change by regulating its stability via promoting protein synthesis and inhibiting degradation, revealed by cycloheximide and MG132 experiments. Collectively, our results suggested that TRF in combination with cisplatin might be an additional novel therapeutic strategy for patients with lung cancer.

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“…Cell migration is closely associated with tumor metastasis [ 12 , 13 ]. Then, the cell migration was detected by scratch wound healing assay.…”

Section: Resultsmentioning

confidence: 99%

Combined time-restricted feeding and cisplatin enhance the anti-tumor effects in cisplatin-resistant and -sensitive lung cancer cells

Chen

Shi

et al. 2022

Med Oncol

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“…Multiple studies have highlighted the regulatory roles of lncRNA through sponging miRNAs and binding proteins [ 9 , 25 ]. To validate whether CEBPA-DT acts as a “miRNA sponge", we conducted the bioinformatic analysis to evaluate the potential binding miRNAs for CEBPA-DT using Starbase [ 26 ].…”

Section: Resultsmentioning

confidence: 99%

LncRNA CEBPA-DT promotes liver cancer metastasis through DDR2/β-catenin activation via interacting with hnRNPC

Cai

Lyu

et al. 2022

J Exp Clin Cancer Res

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Background Hepatocellular carcinoma (HCC) is the world’s third leading cause of cancer-related death; due to the fast growth and high prevalence of tumor recurrence, the prognosis of HCC patients remains dismal. Long non-coding RNA CEBPA-DT, a divergent transcript of the CCAAT Enhancer Binding Protein Alpha (CEBPA) gene, has been shown to participate in multiple tumor progression. However, no research has established its cancer-promoting mechanism in HCC yet. Methods CEBPA-DT was identified in human HCC tissues through RNA sequencing. The expression level of CEBPA-DT was assessed by quantitative real-time PCR. The biological effects of CEBPA-DT were evaluated in vitro and in vivo through gain or loss of function experiments. RNA fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down assays were applied to investigate the downstream target of CEBPA-DT. Immunofluorescence, subcellular protein fractionation, western blot, and co-immunoprecipitation were performed to analyze the subcellular location of β-catenin and its interaction with Discoidin domain-containing receptor 2 (DDR2). Results CEBPA-DT was upregulated in human HCC tissues with postoperative distant metastasis and intimately related to the worse prognosis of HCC patients. Silencing of CEBPA-DT inhibited the growth, migration and invasion of hepatoma cells in vitro and in vivo, while enhancement of CEBPA-DT played a contrasting role. Mechanistic investigations demonstrated that CEBPA-DT could bind to heterogeneous nuclear ribonucleoprotein C (hnRNPC), which facilitated cytoplasmic translocation of hnRNPC, enhanced the interaction between hnRNPC and DDR2 mRNA, subsequently promoted the expression of DDR2. Meanwhile, CEBPA-DT induced epithelial-mesenchymal transition (EMT) process through upregulation of Snail1 via facilitating nuclear translocation of β-catenin. Using DDR2 inhibitor, we revealed that the CEBPA-DT induced the interaction between DDR2 and β-catenin, thus promoting the nuclear translocation of β-catenin to activate transcription of Snail1, contributing to EMT and HCC metastasis. Conclusions Our results suggested that CEBPA-DT promoted HCC metastasis through DDR2/β-catenin mediated activation of Snail1 via interaction with hnRNPC, indicating that the CEBPA-DT-hnRNPC-DDR2/β-catenin axis may be used as a potential therapeutic target for HCC treatment.

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“…LncRNAs are involved in multiple ccRCC regulatory processes, including proliferation, metastasis, immune microenvironment, and immune response [17,20]. LncRNAs have been shown to predict the prognosis of ccRCC patients with good accuracy [21].…”

Section: Discussionmentioning

confidence: 99%

Causal relationship between telomere length and renal cell carcinoma and prognostic modeling of ccRCC based on telomere- related lncRNAs

Chen,

Zeng,

2024

Preprint

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Background Telomeres have been demonstrated to be critical in the development of multiple tumors. However, the association of telomere-related lncRNAs with clear cell renal cell carcinoma (ccRCC) and their prognostic roles in ccRCC patients remain unknown. Methods Exposure data was obtained from GWAS database. Two-sample mendelian randomization (MR) was used to test for causal associations between telomere length and renal cell carcinoma. Expression matrix and clinicopathological data of ccRCC patients were extracted from The Cancer Genome Altas and UCSC Xena browser. The differentially expressed genes were identified and intersected with the telomere-related genes downloaded from the Telnet database. Telomere-related lncRNAs were screened by the univariate Cox regression analysis. Each patient's risk score was calculated to establish a nomogram based on eight telomere-related lncRNAs screened by the least absolute shrinkage and selection operator (LASSO) algorithm and multivariate Cox regression analysis. The correlation between telomere-related lncRNAs and immune cells was assessed by the CIBEERSORT algorithm. The immune and stromal infiltrations were quantified by the ESTIMATE algorithm. Gene set enrichment analysis (GSEA) was performed to explore the selected lncRNA functions. Result A causal relationship between telomere length and renal cell carcinoma was observed. We screened eight telomere-related lncRNAs and established a risk score model for predicting survival in ccRCC patients. A nomogram was developed to predict the survival outcomes of postoperative patients by integrating several clinical factors, and a well-predictive effect was observed. The correlation between selected lncRNAs and immune function was explored by the CIBEERSORT and ESTIMATE algorithms. Besides, GSEA showed that telomere-related lncRNAs could affect ccRCC prognosis through multiple pathways.

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LncRNA MILIP links YBX1 to translational activation of Snai1 and promotes metastasis in clear cell renal cell carcinoma

Cited by 24 publications

References 45 publications

Combined time-restricted feeding and cisplatin enhance the anti-tumor effects in cisplatin-resistant and -sensitive lung cancer cells

Combined time-restricted feeding and cisplatin enhance the anti-tumor effects in cisplatin-resistant and -sensitive lung cancer cells

LncRNA CEBPA-DT promotes liver cancer metastasis through DDR2/β-catenin activation via interacting with hnRNPC

Causal relationship between telomere length and renal cell carcinoma and prognostic modeling of ccRCC based on telomere- related lncRNAs

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