scholarly journals Comprehensive analysis of RNA binding motif protein 3 (RBM3) in non‐small cell lung cancer

2020 ◽  
Vol 9 (15) ◽  
pp. 5609-5619 ◽  
Author(s):  
Annette Salomonsson ◽  
Patrick Micke ◽  
Johanna S. M. Mattsson ◽  
Linnea La Fleur ◽  
Johan Isaksson ◽  
...  
2020 ◽  
Vol 19 ◽  
pp. 153303382097752
Author(s):  
Jianying Zhou ◽  
Dan Xiao ◽  
Tingting Qiu ◽  
Jun Li ◽  
Zhentian Liu

Objective: Extracellular vesicles (Evs) secreted from cells have been revealed to mediate signal transduction between cells. Nevertheless, the mechanisms through which molecules transported by EVs function remain to be elucidated. In the present study, the functional relevance of endothelial cells (ECs)-secreted Evs carrying microRNA-376c (miR-376c) in the biological activities of non-small cell lung cancer (NSCLC) cells was investigated, including the related mechanisms. Methods: Two cell lines with the highest YTH N6-methyladenosine (m6A) RNA binding protein 1 (YTHDF1) expression were selected for subsequent experiments. Cellular proliferation, migration, invasion and apoptosis were measured by EdU, wound healing, Transwell assays and flow cytometry, respectively. The binding relationship between miR-376c and YTHDF1 was analyzed by dual-luciferase reporter assays. The miR-376c, YTHDF1 and β-catenin expression was evaluated by qPCR assays and western blot assays. Results: The expression patterns of YTHDF1 were higher in NSCLC cells, whereas miR-376c was reduced versus the normal bronchial epithelial cells. Silencing of YTHDF1 repressed NSCLC cell proliferation, invasion and migration abilities, whereas enhanced apoptosis. miR-376c negatively modulated YTHDF1 expression. Under co-culture conditions, ECs transmitted miR-376c into NSCLC cells through Evs, and inhibited the intracellular YTHDF1 expression and the Wnt/β-catenin pathway activation. Rescue experiments revealed that YTHDF1 overexpression reversed the inhibitory role of miR-376c released by EC-Evs in NSCLC cells. Conclusion: EC-delivered Evs inhibit YTHDF1 expression and the Wnt/β-catenin pathway induction via miR-376c overexpression, thus inhibiting the malignant phenotypes of NSCLC cells.


2020 ◽  
Vol 117 (8) ◽  
pp. 4347-4357 ◽  
Author(s):  
Guang Liang ◽  
Wei Meng ◽  
Xiangjie Huang ◽  
Wangyu Zhu ◽  
Changtian Yin ◽  
...  

Lung cancer is the leading cause of cancer-related deaths worldwide and non-small cell lung cancer (NSCLC) accounts for over 80% of lung cancer cases. The RNA binding protein, QKI, belongs to the STAR family and plays tumor-suppressive functions in NSCLC. QKI-5 is a major isoform of QKIs and is predominantly expressed in NSCLC. However, the underlying mechanisms of QKI-5 in NSCLC progression remain unclear. We found that QKI-5 regulated microRNA (miRNA), miR-196b-5p, and its expression was significantly up-regulated in NSCLC tissues. Up-regulated miR-196b-5p promotes lung cancer cell migration, proliferation, and cell cycle through directly targeting the tumor suppressors, GATA6 and TSPAN12. Both GATA6 and TSPAN12 expressions were down-regulated in NSCLC patient tissue samples and were negatively correlated with miR-196b-5p expression. Mouse xenograft models demonstrated that miR-196b-5p functions as a potent onco-miRNA, whereas TSPAN12 functions as a tumor suppressor in NSCLC in vivo. QKI-5 bound to miR-196b-5p and influenced its stability, resulting in up-regulated miR-196b-5p expression in NSCLC. Further analysis showed that hypomethylation in the promoter region enhanced miR-196b-5p expression in NSCLC. Our findings indicate that QKI-5 may exhibit novel anticancer mechanisms by regulating miRNA in NSCLC, and targeting the QKI5∼miR-196b-5p∼GATA6/TSPAN12 pathway may enable effectively treating some NSCLCs.


2018 ◽  
Vol 98 (12) ◽  
pp. 1562-1574 ◽  
Author(s):  
Elena Martínez-Terroba ◽  
Teresa Ezponda ◽  
Cristina Bértolo ◽  
Cristina Sainz ◽  
Ana Remírez ◽  
...  

2021 ◽  
Author(s):  
Ming Zhang ◽  
Hualiang Zhang ◽  
Linfeng Cao ◽  
Gouxin Hou ◽  
Chao Lu ◽  
...  

Abstract Background As mRNA binding proteins, MEX3 (muscle excess 3) family highlights its unique characteristics and plays an emerging role in post-transcriptionally regulating programmed of biological processes, including tumor cell death and immunological relevance. These have been shown to be involved in various diseases, however, the role of MEX3 in non-small-cell lung cancer (NSCLC) has not been fully elucidated. Results In this study, we found that the sequence or copy number of MEX3 gene did not change significantly, which can explain the stability of malignant tumor development through the COSMIC database. Further, gene expression in NSCLC was examined using the Oncomine™ database, and the prognostic value of each gene was analyzed by Kaplan-Meier analysis. The results showed that overexpressed of MEX3A, MEX3B, MEX3C and MEX3D were associated with significantly lower OS in patients with NSCLC and LUAD, while overexpressed of MEX3D was associated with significantly poorer OS in patients with LUSC. We also applied the Tumor Immune Estimation Resource (TIMER) tool to assess the correlations between distinct MEX3 and the infiltrating immune cell landscape. Conclusion On this subject, we have learned about the complexity and heterogeneity of NSCLC through MEX3. We found that most of MEX3 is highly expressed in NSCLC. High expression indicates a poor prognosis and has a certain immune correlation. Therefore, these conclusions can lay a framework for the prognosis of NSCLC patients and the development of treatment strategies in the future.


Author(s):  
Kazumi Nishino ◽  
Tadashi Osaki ◽  
Toru Kumagai ◽  
Takashi Kijima ◽  
Isao Tachibana ◽  
...  

2020 ◽  
Author(s):  
Ti-wei Miao ◽  
Fang-ying Chen ◽  
Wei Xiao ◽  
Long-yi Du ◽  
Bing Mao ◽  
...  

Abstract Background: Non-small cell lung cancer (NSCLC) is a malignancy with relatively high incidence and poor prognosis. RNA-binding proteins (RBPs) were reported to be dysregulated in multiple cancers and were closely associated with tumor initiation and progression. However, the functions of RBPs in NSCLC remain unclear. Method: The RNA sequencing data and corresponding clinical information of NSCLC was downloaded from The Cancer Genome Atlas (TCGA) database. We identified aberrantly expressed RBPs between tumor and control tissue, and systemically investigated the expression and prognostic value of these RBPs by a series of bioinformatics analysis.Results: A total of 459 aberrantly expressed RBPs (291 up-regulated and 168 down-regulated RBPs) were identified. Functional enrichment analysis indicated that the differentially expressed RBPs were mainly associated with RNA splicing, ncRNA metabolic process, regulation of translation, mRNA surveillance pathway, RNA degradation, and RNA transport. Thirteen RBPs (ZC3H12C, ZC3H12D, BOP1, CASC3, DDX24, IGF2BP1, KHDC1, FASTKD3, TARBP1, INTS7, NOL12, SNRPB, PABPC1L) were identified as prognostic RBPs by multivariate Cox regression analysis, and were used to construct a prognostic signature. Further analysis demonstrated that high-risk group were significantly related to poor overall survival in training and testing cohort. The area under receiver operator characteristic curve of the prognostic signature was 0.703 in training cohort and 0.636 in testing cohort. In addition, the prognostic signature was further validated in differently clinical subgroup (>=65, <65, female, male, stage I-II, III- IV, T1-2, T3-4, N0, N1-3, M0 and M1). The risk score was an independent prognostic factor of NSCLC. A nomogram based on thirteen RBPs was constructed to predict the survival of patients.Conclusion: Our results provide novel insights into the pathogenesis of NSCLC. The RBPs-associated prognostic signature showed predictive value for NSCLC prognosis, with potential applications in clinical decision-making and individualized treatment.


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