miR-125a-3p targets MTA1 to suppress NSCLC cell proliferation, migration, and invasion

Zhang, Hong; Zhu, Xiaoxia; Li, Na; Li, Dianhe; Zhou, Sha; Zheng, Xuelian; Wang, Haofei

doi:10.1093/abbs/gmv039

Cited by 39 publications

(31 citation statements)

References 41 publications

(33 reference statements)

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“…Further influence was registered in the altered expressions of select microRNAs and transcription factors, all noted for their role in cell phenotype and fate. [52][53][54][55] We further corroborated the utility and feasibility of TI inhibition by the application of the clinically employed eIF4E inhibitor and anti-viral drug ribavirin. [35][36][37][38] Generally, all of our observations are in sync with published data.…”

Section: Discussionmentioning

confidence: 70%

“…29 Interestingly, published data reported that MIR-125a suppresses NSCLC cell proliferation, migration, and invasion. 52 Thus, we tested the expression of MIR-125a in eIF4E/eIF4GI KD NSCLC cell lines by qPCR. Both NSCLC cell lines displayed elevated levels of MIR-125a 48 h post eIF4E/eIF4GI silencing (45-65%↑; Po0.05) (Figure 6a).…”

Section: Eif4e/eif4gi Kds Affected Micrornas With a Possible Role In mentioning

confidence: 99%

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Migration and epithelial-to-mesenchymal transition of lung cancer can be targeted via translation initiation factors eIF4E and eIF4GI

Attar-Schneider

Drucker

Gottfried

2016

Laboratory Investigation

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Metastasis underlies cancer morbidity and accounts for disease progression and significant death rates generally and in non-small cell lung cancer (NSCLC) particularly. Therefore, it is critically important to understand the molecular events that regulate metastasis. Accumulating data portray a central role for protein synthesis, particularly translation initiation (TI) factors eIF4E and eIF4G in tumorigenesis and patients' survival. We have published that eIF4E/eIF4GI activities and consequently NSCLC cell migration are modulated by bone-marrow mesenchymal stem cell secretomes, suggesting a role for TI in metastasis. Here, we aimed to expand our understanding of the TI factors significance to NSCLC characteristics, particularly epithelial-to-mesenchymal transition (EMT) and migration, supportive of metastasis. In a model of NSCLC cell lines (H1299, H460), we inhibited eIF4E/eIF4GI's expressions (siRNA, ribavirin) and assessed NSCLC cell lines' migration (scratch), differentiation (EMT, immunoblotting), and expression of select microRNAs (qPCR). Initially, we determined an overexpression of several TI factors (eIF4E, eIF4GI, eIF4B, and DHX29) and their respective targets in NSCLC compared with normal lung samples (70-350%↑, P<0.05). Knockdown (KD) of eIF4E/eIF4GI in NSCLC cell lines (70%↓, P<0.05) also manifested in decreased target levels (ERα, SMAD5, NFkB, CyclinD1, c-MYC, and HIF1α) (20-50%↓, P<0.05). eIF4E/eIF4GI KD also attenuated cell migration (60-75%↓, P<0.05), EMT promoters (15-90%↓, P<0.05), and enhanced EMT suppressors (30-380%↑, P<0.05). The importance of eIF4E KD to NSCLC phenotype was further corroborated with its inhibitor, ribavirin. Changes in expression of essential microRNAs implicated in NSCLC cell migration concluded the study (20-100%, P<0.05). In summary, targeting eIF4E/eIF4GI reduces migration and EMT, both essential for metastasis, thereby underscoring the potential of TI targeting in NSCLC therapy, especially the already clinically employed agents (ribavirin/4EGI). Comparison of these findings with previously reported effects of eIF4E/eIF4GI KD in multiple myeloma suggests a collective role for these TI factors in cancer progression.

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Section: Discussionmentioning

confidence: 70%

Section: Eif4e/eif4gi Kds Affected Micrornas With a Possible Role In mentioning

confidence: 99%

Migration and epithelial-to-mesenchymal transition of lung cancer can be targeted via translation initiation factors eIF4E and eIF4GI

Attar-Schneider

Drucker

Gottfried

2016

Laboratory Investigation

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“…Among these three miRNAs, MiR-125a-3p expression levels has been reported to be lower in NSCLC tissues when compared with normal lung tissues and were associated with poor prognoses in NSCLC [36]. MiR-125a-3p inhibited the proliferation, migration, and invasion of NSCLC cells [37,38]. MiR-371-5p played an important role of "oncosuppressor" in colorectal cancer progression in the regulation of EMT, stemness and metastasis [39].…”

Section: Discussionmentioning

confidence: 99%

The permissive role of TCTP in PM2.5/NNK-induced epithelial–mesenchymal transition in lung cells

et al. 2020

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Background: Translationally controlled tumor protein (TCTP) is linked to lung cancer. However, upon lung cancer carcinogens stimulation, there were no reports on the relationship between TCTP and lung cell carcinogenic epithelial-mesenchymal transition (EMT). This study was designed to investigate the molecular mechanism of regulation of TCTP expression and its role in lung carcinogens-induced EMT. Methods:To study the role of TCTP in lung carcinogens [particulate matter 2.5 (PM 2.5 ) or 4-methylnitrosamino-l-3-pyridyl-butanone (NNK)]-induced EMT, PM 2.5 /NNK-treated lung epithelial and non-small cell lung cancer (NSCLC) cells were tested. Cell derived xenografts, human lung cancer samples and online survival analysis were used to confirm the results. MassArray assay, Real-time PCR and Reporter assays were performed to elucidate the mechanism of regulation of TCTP expression. All statistical analyses were performed using GraphPad Prism version 6.0 or SPSS version 20.0.Results: Translationally controlled tumor protein and vimentin expression were up-regulated in PM 2.5 /NNK-treated lung cells and orthotopic implantation tumors. TCTP expression was positively correlated with vimentin in human NSCLC samples. Patients with high expression of TCTP displayed reduced overall and disease-free survival. TCTP overexpression could increase vimentin expression and promote cell metastasis. Furthermore, PM 2.5 /NNK stimulation brought a synergistic effect on EMT in TCTP-transfected cells. TCTP knockdown blocked PM 2.5 /NNK carcinogenic effect. Mechanically, PM 2.5 /NNK-induced TCTP expression was regulated by one microRNA, namely miR-125a-3p, but not by methylation on TCTP gene promoter. The level of TCTP was regulated by its specific microRNA during the process of PM 2.5 /NNK stimulation, which in turn enhanced vimentin expression and played a permissive role in carcinogenic EMT. Conclusions:Our results provided new insights into the mechanisms of TCTP regulatory expression in lung carcinogens-induced EMT. TCTP and miR-125a-3p might act as potential prognostic biomarkers and therapeutic targets for NSCLC.© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'

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“…Higher expression of miR-125a may predict better survival in NSCLC patients. 14,[34][35][36][37] Wang et al reported that miR-125a, as a metastatic suppressor in lung cancer cells, activated by epidermal growth factor receptor (EGFR) signaling, inhibits tumorigenesis and tube formation. 38 In our study, rs8111742 located 1033bp upstream of miR-125a was associated with better survival in NSCLC patients.…”

Section: F I G U R E 1 Kaplan-meier Plots Of Survival According Tomentioning

confidence: 99%

Genetic variations in miR‐125 family and the survival of non‐small cell lung cancer in Chinese population

Shen

Yang

et al. 2019

Cancer Medicine

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To investigate the associations between the functional single nucleotide polymorphisms (SNPs) in the miR‐125 family and the survival of non‐small cell lung cancer (NSCLC) patients, we systematically selected six functional SNPs located in three pre‐miRNAs (miR‐125a, miR‐125b‐1, miR‐125b‐2). Cox proportional hazard regression analyses were conducted to estimate the crude and adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs). Reporter gene luciferase assay was performed to examine the relationship between the SNPs and transcriptive activity of the miRNAs. The expression of miRNAs in different cells was detected using quantitative real‐time PCR assay. We found that rs2241490 (upstream of miR‐125b‐1, G > A, adjusted HR = 1.24, 95%CI = 1.05‐1.48, P = 0.014, in dominant model; adjusted HR = 1.18, 95%CI = 1.03‐1.35, P = 0.014, in additive model), rs512932 (upstream of miR‐125b‐1, A > G, dominant model: adjusted HR = 1.25, 95%CI = 1.05‐1.48, P = 0.013) and rs8111742 (upstream of miR‐125a, G > A, dominant model: adjusted HR = 0.84, 95%CI = 0.71‐1.00, P = 0.047) were associated with the prognosis of 1001 Chinese NSCLC patients. The combined analysis of the three SNPs related the number of risk alleles (rs2241490‐A, rs512932‐G and rs8111742‐G) to death risk of NSCLC in a locus‐dosage mode ( P for trend <0.001). Furthermore, luciferase reporter gene assay showed significantly higher levels of luciferase activity with rs512932 variant G than that with A allele in 293T, SPC‐A1 and A549 cell lines. Besides, miR‐125b was highly expressed in lung cancer cells than the normal lung cell. Our study indicated that genetic variations in miR‐125 family were implicated in the survival of NSCLC patients. Larger population‐based and functional studies are needed to verify these findings.

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miR-125a-3p targets MTA1 to suppress NSCLC cell proliferation, migration, and invasion

Cited by 39 publications

References 41 publications

Migration and epithelial-to-mesenchymal transition of lung cancer can be targeted via translation initiation factors eIF4E and eIF4GI

Migration and epithelial-to-mesenchymal transition of lung cancer can be targeted via translation initiation factors eIF4E and eIF4GI

The permissive role of TCTP in PM2.5/NNK-induced epithelial–mesenchymal transition in lung cells

Genetic variations in miR‐125 family and the survival of non‐small cell lung cancer in Chinese population

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