MicroRNA-32-5p inhibits epithelial-mesenchymal transition and metastasis in lung adenocarcinoma by targeting SMAD family 3

Zhang, Jinxing; Wu, Yang; Wu, Jun-Zheng; Zhou, Chun Hui; Liu, Sheng; Shi, Haibin; Zhou, Wei-Zhong

doi:10.7150/jca.48387

Cited by 18 publications

(11 citation statements)

References 36 publications

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“…Through mRNA-miRNA-lncRNA network construction, the lncRNA KCNQ1OT1 / hsa-miRNA-32-5p / PER2 / CRY2 regulatory axis was identified. Previous studies have reported that miRNA-32-5p regulates the progression of gastric cancer and epithelial-mesenchymal transition and metastasis in lung adenocarcinoma [ 43 , 44 ]. However, studies concerning the role of miRNA-32-5p in COAD are lacking.…”

Section: Discussionmentioning

confidence: 99%

Circadian Clock Genes Are Correlated with Prognosis and Immune Cell Infiltration in Colon Adenocarcinoma

Huang

Zhang

et al. 2022

Computational and Mathematical Methods in Medicine

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Background. Colon adenocarcinoma (COAD) is a malignancy with a high incidence and is associated with poor quality of life. Dysfunction of circadian clock genes and disruption of normal rhythms are associated with the occurrence and progression of many cancer types. However, studies that systematically describe the prognostic value and immune-related functions of circadian clock genes in COAD are lacking. Methods. Genomic data obtained from The Cancer Genome Atlas (TCGA) database was analyzed for expression level, mutation status, potential biological functions, and prognostic performance of core circadian clock genes in COAD. Their correlations with immune infiltration and TMB/MSI score were analyzed by Spearman’s correlation analysis. Pearson’s correlation analysis was performed to analyze their associations with drug sensitivity. Lasso Cox regression analysis was performed to construct a prognosis signature. Moreover, an mRNA-miRNA-lncRNA regulatory axis was also detected by ceRNA network. Results. In COAD tissues, the mRNA levels of CLOCK, CRY1, and NR1D1 were increased, while the mRNA levels of ARNTL, CRY2, PER1, PER3, and RORA were decreased. We also summarized the relative genetic mutation variation landscape. GO and KEGG pathway analyses demonstrated that these circadian clock genes were primarily correlated with the regulation of circadian rhythms and glucocorticoid receptor signaling pathways. COAD patients with high CRY2, NR1D1, and PER2 expression had worse prognosis. A prognostic model constructed based on the 9 core circadian clock genes predicted the COAD patients’ overall survival with medium to high accuracy. A significant association between prognostic circadian clock genes and immune cell infiltration was found. Moreover, the lncRNA KCNQ1OT1/hsa-miRNA-32-5p/PER2/CRY2 regulatory axis in COAD was also detected through a mRNA-miRNA-lncRNA network. Conclusion. Our results identified CRY2, NR1D1, and PER2 as potential prognostic biomarkers for COAD patients and correlated their expression with immune cell infiltration. The lncRNA KCNQ1OT1/hsa-miRNA-32-5p/PER2/CRY2 regulatory axis was detected in COAD and might play a vital role in the occurrence and progression of COAD.

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Section: Discussionmentioning

confidence: 99%

Circadian Clock Genes Are Correlated with Prognosis and Immune Cell Infiltration in Colon Adenocarcinoma

Huang

Zhang

et al. 2022

Computational and Mathematical Methods in Medicine

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“…On the contrary, miRNAs may also inhibit metastasis. MiRNA-32-5p inhibits EMT and metastasis in lung adenocarcinoma by targeting SMAD3 ( Zhang J.-X. et al, 2021 ), miR-16-1-3p suppresses breast cancer growth and metastasis by inhibiting Warburg Effect ( Ye et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Cancer-Associated Fibroblasts Promote Migration and Invasion of Non-Small Cell Lung Cancer Cells via miR-101-3p Mediated VEGFA Secretion and AKT/eNOS Pathway

Guo

Chen

Cao

et al. 2021

Front. Cell Dev. Biol.

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Cancer-associated fibroblasts (CAFs) are major component of tumor microenvironment (TME), which plays crucial roles in tumor growth, invasion and metastasis; however, the underling mechanism is not fully elucidated. Despite many studies are focused on the tumor promoting effect of CAFs-derived cytokines, the upstream regulators of cytokine release in CAFs is largely unknown. Here we found that miR-101-3p was downregulated in primary lung cancer-associated CAFs compared to normal fibroblasts (NFs). Ectopic overexpression of miR-101-3p suppressed CAFs activation, and abrogated the promoting effect of CAFs on migration and invasion of non-small cell lung cancer cells (NSCLC), through attenuating CAFs’ effect on epithelial mesenchymal transition (EMT) process, metastasis-related genes (MMP9, TWIST1) and AKT/endothelial nitric oxide synthase (eNOS) signaling pathway. Further study indicated that vascular endothelial growth factor A (VEGFA) was a novel target of miR-101-3p, and CAFs-derived VEGFA mediated the effect of miR-101-3p on migration and invasion of lung cancer cells, demonstrated by using recombinant VEGFA and VEGFA neutralizing antibody. Interestingly, the analysis of the Cancer Genome Atlas (TCGA) database revealed that lung cancer tissues expressed lower level of miR-101-3p than non-cancerous tissues, and low/medium-expression of miR-101-3p was associated with poor overall survival (OS) rate. Moreover, the mouse xenograft experiment also showed that CAFs accelerated tumor growth whereas miR-101-3p diminished CAFs’ effect. These findings revealed a novel mechanism that CAFs facilitated lung cancer metastasis potential via miR-101-3p/VEGFA/AKT signaling pathway, suggesting miR-101-3p as a potential candidate for metastasis therapy.

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“…A previous study showed that knockdown of NEAT1 promotes apoptosis by sponging miR-153-3p, thereby inhibiting cell proliferation, migration, and invasion in NSCLC [40]. miRNA-32-5p has been reported to inhibit epithelial-mesenchymal transition (EMT) and metastasis in LUAD by targeting SMAD family 3 (SMAD3) [41]. In addition, the expression of miR-890 was negatively regulated by small nucleolar host gene 3 (SNHG3).…”

Section: Discussionmentioning

confidence: 99%

m7G-related miRNA signature for prediction of prognosis in lung adenocarcinoma

Jiang

Shi

Xiao

et al. 2022

Preprint

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Background N7-methylguanosine (m7G), one of the most conserved nucleotide modifications, presents in mRNA caps and internal sites of tRNAs and rRNAs. Previous data have demonstrated that abnormal m7G is associated with tumorigenesis. Notably, the expression of m7G’s regulators remains unknown in human cancers, especially in lung adenocarcinoma (LUAD). This study aimed to construct a prognostic signature based on m7G-related miRNAs in LUAD and to explore the potential association of the regulators with tumor immune microenvironment (TIME). Methods We used LUAD data from The Cancer Genome Atlas (TCGA) to establish a risk model based on the m7G-related miRNAs, and divided patients into high-risk or low-risk subgroups. A nomogram for predicting overall survival (OS) was then constructed based on the independent risk factors. In addition, we performed functional enrichment analysis and defined the immune landscape as well as drug response profile in the high-risk and low-risk subgroups. Results This study incorporated 28 m7G-related miRNAs into the risk model. The data showed a significant difference in the OS between the high-risk and low-risk subgroups. The receiver operating characteristic curve (ROC) predicted that the area under the curve (AUC) of 1-year, 3-year and 5-year OS was 0.781, 0.804 and 0.853, respectively. The C-index of the prognostic nomogram for predicting OS was 0.739. We then analyzed the immune landscape in the high-risk and low-risk subgroups. The data demonstrated significant differences in the estimated score, immune score, stromal score, immune cell infiltration and functions between the high-risk and low-risk subgroups. In addition, drug response analysis showed that low-risk subgroups may be more sensitive to tyrosine kinase inhibitor (TKI) and histone deacetylase (HDAC) inhibitors. Conclusion We successfully developed a novel risk model based on m7G-related miRNAs in this study. The model can predict clinical prognosis and guide therapeutic regimens in patients with LUAD. Our data also provided new insights into molecular mechanisms of m7G in LUAD.

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MicroRNA-32-5p inhibits epithelial-mesenchymal transition and metastasis in lung adenocarcinoma by targeting SMAD family 3

Cited by 18 publications

References 36 publications

Circadian Clock Genes Are Correlated with Prognosis and Immune Cell Infiltration in Colon Adenocarcinoma

Circadian Clock Genes Are Correlated with Prognosis and Immune Cell Infiltration in Colon Adenocarcinoma

Cancer-Associated Fibroblasts Promote Migration and Invasion of Non-Small Cell Lung Cancer Cells via miR-101-3p Mediated VEGFA Secretion and AKT/eNOS Pathway

m7G-related miRNA signature for prediction of prognosis in lung adenocarcinoma

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