Deregulated MicroRNAs in Cancer-Associated Fibroblasts from Front Tumor Tissues of Lung Adenocarcinoma as Potential Predictors of Tumor Promotion

Negrete-García, María Cristina; Ramírez-Rodríguez, Sandra Lizbeth; Rangel‐Escareño, Claudia; Muñoz-Montero, Said; Kelly-García, Javier; Vázquez-Manriquez, María Eugenia; Santillán, Patricio; Ramírez, Martha Montaño; Ramírez-Martínez, Gustavo; Ramírez‐Venegas, Alejandra; Ortiz‐Quintero, Blanca

doi:10.1620/tjem.246.107

Cited by 11 publications

(9 citation statements)

References 70 publications

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“…When the differentially expressed miRNAs were subjected to univariate Cox proportional hazard regression analysis, Lin et al pointed out that miR-1468 ( P = 0.009) and miR-3653 ( P = 0.012) were significantly correlated with recurrence-free survival (RFS) of LUAD ( Lin et al, 2016 ). The down-regulated expression of miR-299 in LUAD has been reported to serve as a functional role in therapeutic efficacy, including gefitinib resistance and chemoresistance ( Negrete-Garcia et al, 2018 ; Li et al, 2018 ; Zheng et al, 2015 ). Through miR-299-3p/TNFSF12 pathway, RHPN1-AS1 could modulate the LUAD therapeutic resistance to gefitinib ( Li et al, 2018 ), and the suppression of ABCE1 could affect the sensitivity of LC to doxorubicin ( Zheng et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Construction and validation of a novel prognostic signature of microRNAs in lung adenocarcinoma

Liu

et al. 2021

PeerJ

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MicroRNA (miRNA, miR) has been reported to be highly implicated in a wide range of biological processes in lung cancer (LC), and identification of differentially expressed miRNAs between normal and LC samples has been widely used in the discovery of prognostic factors for overall survival (OS) and response to therapy. The present study was designed to develop and evaluate a miRNA-based signature with prognostic value for the OS of lung adenocarcinoma (LUAD), a common histologic subtype of LC. In brief, the miRNA expression profiles and clinicopathological factors of 499 LUAD patients were collected from The Cancer Genome Atlas (TCGA) database. Kaplan–Meier (K-M) survival analysis showed significant correlations between differentially expressed miRNAs and LUAD survival outcomes. Afterward, 1,000 resample LUAD training matrices based on the training set was applied to identify the potential prognostic miRNAs. The least absolute shrinkage and selection operator (LASSO) cox regression analysis was used to constructed a six-miRNA based prognostic signature for LUAD patients. Samples with different risk scores displayed distinct OS in K-M analysis, indicating considerable predictive accuracy of this signature in both training and validation sets. Furthermore, time-dependent receiver operating characteristic (ROC) analysis demonstrated the nomogram achieved higher predictive accuracy than any other clinical variables after incorporating the clinical information (age, sex, stage, and recurrence). In the stratification analysis, the prognostic value of this classifier in LUAD patients was validated to be independent of other clinicopathological variables, such as age, gender, tumor recurrence, and early stage. Gene set annotation analyses were also conducted through the Hallmark gene set and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, indicating target genes of the six miRNAs were positively related to various molecular pathways of cancer, such as hallmark UV response, Wnt signaling pathway and mTOR signaling pathway. In addition, fresh cancer tissue samples and matched adjacent tissue samples from 12 LUAD patients were collected to verify the expression of miR-582’s target genes in the model, further revealing the potential relationship between SOX9, RASA1, CEP55, MAP4K4 and LUAD tumorigenesis, and validating the predictive value of the model. Taken together, the present study identified a robust signature for the OS prediction of LUAD patients, which could potentially aid in the individualized selection of therapeutic approaches for LUAD patients.

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Section: Discussionmentioning

confidence: 99%

Construction and validation of a novel prognostic signature of microRNAs in lung adenocarcinoma

Liu

et al. 2021

PeerJ

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“…notably, the present study revealed that knockout of mirna-455-3p promoted invasion of lncaP cells. it was reported that mir-505 functions as a tumor suppressor in endometrial cancer by targeting tumor growth factor α and mir-505 modulated cancer proliferation and migration in human non-small cell lung cancer through inverse regulation of FZD4 (37). However, the functions remain to be elucidated in human Pca.…”

Section: Discussionmentioning

confidence: 99%

Functional classification of prostate cancer‑associated miRNAs through CRISPR/Cas9‑mediated gene knockout

et al. 2020

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The aim of the present study was to use the clustered regularly interspaced short palindromic repeats (criSPr) and criSPr-associated (cas) 9-mediated gene knockout technology for the rapid classification of the differential function of micro (mi)rnas screened using mirna expression profiling by microarray. The rational design of single guide rnas for the criSPr/Cas9 system was verified to function in human LNCaP cells with rapid and efficient target gene editing. mirna (mir)-205, mir-221, mir-222, mir-30c, mir-224, mir-455-3p, mir-23b and mir-505 were downregulated in patients with prostate cancer (Pca) and were experimentally validated to function as tumor suppressors in prostate cancer cells, affecting tumor proliferation, invasion and aerobic glycolysis. in addition, the data of the present study suggested that miR-663a and mfiR-1225-5p were upregulated in prostate cancer tissues and cell proliferation of mir-663a and miR-1225-5p knockout PCa cells was significantly lower compared with mir-nc cells. Furthermore, knockout of miR-1225-5p and miR-663a significantly decreased the lactate production in lncaP cells in vitro. in conclusion, the present study offered a simple and efficient method for rapidly classifying mirna function by applying criSPr/cas9 in lncaP cells. The present study suggested, for the first time to the best of the authors' knowledge, that the aberrant expression of mir-663a and mir-1225-5p may be involved with the progression of prostate cancer, implying their potential as candidate markers for this type of cancer. However, the precise role of mir-663a and mir-1225-5p in accelerating the development of prostate cancer and promoting tumor progression remains to be elucidated.

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“…Of note, miR-299-3p was recently revealed by transcriptomic profiling to be the third-most downregulated miRNA in cancer-associated fibroblasts (CAFs) in lung adenocarcinoma (33). Due to the notable tumor-promoting properties of CAFs, the downregulation of miR-299-3p may modulate the niche, favoring cancer cell invasion and proliferation.…”

Section: Discussionmentioning

confidence: 99%

Tumor‑suppressive miR‑299‑3p inhibits gastric cancer cell invasion by targeting heparanase

Zhou

2019

Mol Med Report

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Gastric cancer (Gc) remains a leading cause of cancer-associated mortality globally. emerging evidence suggests that micrornas (mirs) function as oncogenes or tumor suppressors, contributing to various aspects of cancer progression, including invasion and metastasis. in the present study, the specific role of miR-299-3p in the invasion of GC cells was investigated. The expression level of miR-299-3p was measured using reverse transcription-quantitative Pcr and in situ hybridization in human Gc tissues. effects of miR-299-3p on GC cell invasion were determined by Transwell assay. Bioinformatics and luciferase reporter assays were performed to identify and verify the downstream effectors of miR-299-3p. miR-299-3p expression analysis in clinical GC samples revealed a significant downregulation of miR-299-3p compared with non-tumor tissues. Inhibition of miR-299-3p promoted the invasive abilities of Gc cells, whereas its overexpression significantly suppressed cell invasion. Bioinformatics and luciferase reporter assays identified heparanase (HPSE) as a direct target of miR-299-3p, the ectopic expression of which reversed the impairment in cell invasion induced by miR-299-3p upregulation. Furthermore, HPSE expression was negatively associated with miR-299-3p levels in human GC tissues. Overall, the present study indicated that miR-299-3p functions as a tumor suppressor by directly targeting HPSE, highlighting its potential as a target for the treatment of Gc.

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Deregulated MicroRNAs in Cancer-Associated Fibroblasts from Front Tumor Tissues of Lung Adenocarcinoma as Potential Predictors of Tumor Promotion

Cited by 11 publications

References 70 publications

Construction and validation of a novel prognostic signature of microRNAs in lung adenocarcinoma

Construction and validation of a novel prognostic signature of microRNAs in lung adenocarcinoma

Functional classification of prostate cancer‑associated miRNAs through CRISPR/Cas9‑mediated gene knockout

Tumor‑suppressive miR‑299‑3p inhibits gastric cancer cell invasion by targeting heparanase

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