High expression of miR-493-5p positively correlates with clinical prognosis of non small cell lung cancer by targeting oncogene ITGB1

Zhu, Liang; Kong, Rui; He, Zhan; Lin, Liyao; Qin, Shanshan; Chen, Chun-Yuan; Xie, Zhanqiang; Yu, Fei; Sun, Guo-Qian; Li, Chunguang; Fu, Da; Jiang, Gengxi; Chen, Jie; Ma, Yu‐Shui

doi:10.18632/oncotarget.17650

Cited by 33 publications

(31 citation statements)

References 24 publications

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“…Downregulated expression of miR-190 inhibits the metastasis of breast cancer via inversely regulating the expression of SMAD family member 2 (SMAD2), which is correlated with the prog-nosis of patients with breast cancer (27). By targeting integrin, beta 1 (ITGB1), miR-493-5p plays a prognostic role in NSCLC and could be used to diagnose the disease (28). Four upregulated miRNAs and two downregulated miR- NAs (including miR-218-5p) were identified in lung adenocarcinoma (LUAD) tissues and may represent promising diagnostic and prognostic markers for patients with LUAD (29).…”

Section: Discussionmentioning

confidence: 99%

miR-190, CDK1, MCM10 and NDC80 predict the prognosis of the patients with lung cancer

Gao

Wang²

2019

Revista Romana De Medicina De Laborator

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Lung cancer (LC), which includes small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC), is common and has a high fatality rate. This study aimed to reveal the prognostic mechanisms of LC. GSE30219 was extracted from the Gene Expression Omnibus (GEO) database, and included 293 LC samples and 14 normal lung samples. Differentially expressed genes (DEGs) were identified using the Limma package, and subjected to pathway enrichment analysis using DAVID. MicroRNAs (miRNAs) targeting the DEGs were predicted using Webgestalt. Cytoscape software was used to build a protein-protein interaction (PPI) network and to identify significant network modules. Survival analysis was conducted using Survminer and Survival packages, and validation was performed using The Cancer Genome Atlas (TCGA) dataset. The good and poor prognosis groups contained 518 DEGs. miR-190, miR-493, and miR-218 for the upregulated genes and miR-302, miR-200, and miR-26 for the downregulated genes were predicted. Three network modules (module 1, 2, and 3) were identified from the PPI network. CDK1, MCM10, and NDC80 were the core nodes of module 1, 2, and 3, respectively. In module 1, CDK1 interacted with both CCNB1 and CCNB2. Additionally, CDK1, CCNB1, CCNB2, MCM10, and NDC80 expression levels correlated with clinical survival and were identified as DEGs in both GSE30219 and the TCGA dataset. miR-190, miR-493, miR-218, miR-200, and miR-302 might act in LC by targeting the DEGs. CDK1, CCNB1, CCNB2, MCM10, and NDC80 might also influence the prognosis of LC.

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Section: Discussionmentioning

confidence: 99%

miR-190, CDK1, MCM10 and NDC80 predict the prognosis of the patients with lung cancer

Gao

Wang²

2019

Revista Romana De Medicina De Laborator

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“…mir-493-5p has been previously implicated in the process of carcinogenesis by regulating a number of target genes, including c-MET, EGFR (Wang et al, 2017), integrin subunit beta 1 (ITGB1) (Liang et al, 2017), and fucosyltransferase IV (FUT4) (Zhao et al, 2016) in various tumor types, including breast, prostate, and lung cancers. However, no previous implication of miR-493-5p in DNA repair or responsiveness to chemotherapy has been reported.…”

Section: Discussionmentioning

confidence: 99%

Multifaceted Impact of MicroRNA 493-5p on Genome-Stabilizing Pathways Induces Platinum and PARP Inhibitor Resistance in BRCA2-Mutated Carcinomas

et al. 2018

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SUMMARY BRCA1/2-mutated ovarian cancers (OCs) are defective in homologous recombination repair (HRR) of double-strand breaks (DSBs) and thereby sensitive to platinum and PARP inhibitors (PARPis). Multiple PARPis have recently received US Food and Drug Administration (FDA) approval for treatment of OCs, and resistance to PARPis is a major clinical problem. Utilizing primary and recurrent BRCA1/2-mutated carcinomas from OC patients, patient-derived lines, and an in vivo BRCA2-mutated mouse model, we identified a microRNA, miR-493-5p, that induced platinum/PARPi resistance exclusively in BRCA2-mutated carcinomas. However, in contrast to the most prevalent resistance mechanisms in BRCA mutant carcinomas, miR-493-5p did not restore HRR. Expression of miR-493-5p in BRCA2-mutated/depleted cells reduced levels of nucleases and other factors involved in maintaining genomic stability. This resulted in relatively stable replication forks, diminished single-strand annealing of DSBs, and increased R-loop formation. We conclude that impact of miR-493-5p on multiple pathways pertinent to genome stability cumulatively causes PARPi/platinum resistance in BRCA2 mutant carcinomas.

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“…Of note, eIF4E was a predicted target for miR-338-5p, which showed statistically significant change, as well as miR-31 and miR-182. In addition, miR-493-5p has been previously reported as prognostic marker for overall survival of patients with lung cancer, while miR-21 has been found to induce cell proliferation by targeting TGFBI [ 43 , 44 ]. On the other hand, predicted targets of the miR-139-5p and miR-26a-5p included, among others, genes involved in the MAPK pathway, as well as genes of cell cycle regulation.…”

Section: Resultsmentioning

confidence: 99%

Contribution of miRNAs, tRNAs and tRFs to Aberrant Signaling and Translation Deregulation in Lung Cancer

Skeparnias

Anastasakis

Grafanaki

et al. 2020

Cancers

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Transcriptomics profiles of miRNAs, tRNAs or tRFs are used as biomarkers, after separate examination of several cancer cell lines, blood samples or biopsies. However, the possible contribution of all three profiles on oncogenic signaling and translation as a net regulatory effect, is under investigation. The present analysis of miRNAs and tRFs from lung cancer biopsies indicated putative targets, which belong to gene networks involved in cell proliferation, transcription and translation regulation. In addition, we observed differential expression of specific tRNAs along with several tRNA-related genes with possible involvement in carcinogenesis. Transfection of lung adenocarcinoma cells with two identified tRFs and subsequent NGS analysis indicated gene targets that mediate signaling and translation regulation. Broader analysis of all major signaling and translation factors in several biopsy specimens revealed a crosstalk between the PI3K/AKT and MAPK pathways and downstream activation of eIF4E and eEF2. Subsequent polysome profile analysis and 48S pre-initiation reconstitution experiments showed increased global translation rates and indicated that aberrant expression patterns of translation initiation factors could contribute to elevated protein synthesis. Overall, our results outline the modulatory effects that possibly correlate the expression of important regulatory non-coding RNAs with aberrant signaling and translation deregulation in lung cancer.

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High expression of miR-493-5p positively correlates with clinical prognosis of non small cell lung cancer by targeting oncogene ITGB1

Cited by 33 publications

References 24 publications

miR-190, CDK1, MCM10 and NDC80 predict the prognosis of the patients with lung cancer

miR-190, CDK1, MCM10 and NDC80 predict the prognosis of the patients with lung cancer

Multifaceted Impact of MicroRNA 493-5p on Genome-Stabilizing Pathways Induces Platinum and PARP Inhibitor Resistance in BRCA2-Mutated Carcinomas

Contribution of miRNAs, tRNAs and tRFs to Aberrant Signaling and Translation Deregulation in Lung Cancer

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