Abstract:Background
Accumulating evidence shows that microRNAs are aberrantly expressed and exert essential roles in the tumorigenesis and tumor progression of non‐small cell lung cancer (NSCLC).
Methods
The plasma miRNAs from five healthy donors and four NSCLC patients were profiled by miRNA microarray. The differentially expressed miRNAs from 154 primary NSCLC patients and 146 healthy donors were subjected to RNA isolation and verified by quantitative PCR (qPCR).
Results
The miRNA microarray analysis revealed that 40… Show more
“…Many of the miRNAs, which we detected as significantly regulated in melanoma, are already described in the literature as relevant for the development of other cancers [69,70] or are known to be dysregulated in melanoma, but without a distinctly described molecular function [17,71]. The analysis of their potential target genes and involved pathways in our study allows interesting conclusions to be drawn about their role in melanoma tumorigenesis.…”
Malignant melanoma is one of the most dangerous tumor types due to its high metastasis rates and a steadily increasing incidence. During tumorigenesis, the molecular processes of embryonic development, exemplified by epithelial–mesenchymal transition (EMT), are often reactivated. For melanoma development, the exact molecular differences between melanoblasts, melanocytes, and melanoma cells are not completely understood. In this study, we aimed to identify microRNAs (miRNAs) that promote melanoma tumorigenesis and progression, based on an in vitro model of normal human epidermal melanocyte (NHEM) de-differentiation into melanoblast-like cells (MBrCs). Using miRNA-sequencing and differential expression analysis, we demonstrated in this study that a majority of miRNAs have an almost equal expression level in NHEMs and MBrCs but are significantly differentially regulated in primary tumor- and metastasis-derived melanoma cell lines. Further, a target gene analysis of strongly regulated but functionally unknown miRNAs yielded the implication of those miRNAs in many important cellular pathways driving malignancy. We hypothesize that many of the miRNAs discovered in our study are key drivers of melanoma development as they account for the tumorigenic potential that differentiates melanoma cells from proliferating or migrating embryonic cells.
“…Many of the miRNAs, which we detected as significantly regulated in melanoma, are already described in the literature as relevant for the development of other cancers [69,70] or are known to be dysregulated in melanoma, but without a distinctly described molecular function [17,71]. The analysis of their potential target genes and involved pathways in our study allows interesting conclusions to be drawn about their role in melanoma tumorigenesis.…”
Malignant melanoma is one of the most dangerous tumor types due to its high metastasis rates and a steadily increasing incidence. During tumorigenesis, the molecular processes of embryonic development, exemplified by epithelial–mesenchymal transition (EMT), are often reactivated. For melanoma development, the exact molecular differences between melanoblasts, melanocytes, and melanoma cells are not completely understood. In this study, we aimed to identify microRNAs (miRNAs) that promote melanoma tumorigenesis and progression, based on an in vitro model of normal human epidermal melanocyte (NHEM) de-differentiation into melanoblast-like cells (MBrCs). Using miRNA-sequencing and differential expression analysis, we demonstrated in this study that a majority of miRNAs have an almost equal expression level in NHEMs and MBrCs but are significantly differentially regulated in primary tumor- and metastasis-derived melanoma cell lines. Further, a target gene analysis of strongly regulated but functionally unknown miRNAs yielded the implication of those miRNAs in many important cellular pathways driving malignancy. We hypothesize that many of the miRNAs discovered in our study are key drivers of melanoma development as they account for the tumorigenic potential that differentiates melanoma cells from proliferating or migrating embryonic cells.
“…21 Of note, circulating miR-105-5p might serve as a diagnostic or prognostic biomarker for non-small cell lung cancer or triple negative BC. 22,23 These studies support our findings that miR-105-5p may be related to GI and has the potential as a biomarker for cancer. Upregulation of miR-767-5p was associated with poor prognosis and disease progression in hepatocellular carcinoma.…”
BackgroundBreast cancer (BC) is the most common cancer among women worldwide and a leading cause of cancer‐associated deaths among women. However, there is a lack of accurate prognostic biomarkers for BC. In the present study, we aimed to identify a genomic instability (GI)‐associated microRNA signature as a novel potential prognostic biomarker in BC.MethodsWe performed an integrative analysis to investigate the relationship between GI and BC and identify GI‐associated microRNAs (miRNAs). Subsequently, we conducted a discovery and validation study using multicenter cohorts. The GI‐associated miRNA signature was developed in the discovery cohort and independently validated in internal and external cohorts.ResultsGI‐associated miRNAs expression in BC showed heterogeneity and was significantly correlated with BC prognosis. We identified a GI‐associated two‐miRNA signature (miR‐105‐5p and miR‐767‐5p), termed GI2miR, that stratified BC patients into high‐risk and low‐risk groups with significantly different clinical outcomes (log‐rank p = 0.027) in The Cancer Genome Atlas (TCGA) discovery cohort (n = 763). The prognostic value of GI2miR was further validated in internal TCGA validation cohort (n = 253) (log‐rank p = 0.035) and independent GSE22216 cohort (n = 210) (log‐rank p = 0.036). The GI2miR demonstrated independent prognostic value in multivariate Cox proportional hazard regression analyses and stratification analysis.ConclusionsWe have developed a novel prognostic signature based on GI‐associated two miRNAs for BC, which may lay the foundation for BC to improve prognosis prediction.
“… 30 , 31 A high plasma miR-105 level resulted in poor prognosis of NSCL and was a potential biomarker for early diagnosis of NSCL. 32 In addition, miR-105 was inhibited by LINC00261 and affected the metastasis and proliferation of NSCLC. 33 Consistent with previous reports, our results revealed that miR-873 and miR-105-2 shorten the survival time of LUAD patients by altering the relative proportions of TICs in the TME.…”
Background
Lung adenocarcinoma (LUAD) accounts for approximately 40% of all lung cancer cases. The tumour microenvironment (TME) and microRNAs affect the occurrence, metastasis, recurrence and treatment of tumours. However, the role of microRNAs in the TME and LUAD still needs to be further investigated.
Methods
RNA-seq and microRNA-seq data of LUAD and NSCLC samples were downloaded from the TCGA and GEO database. The immune and stromal components in the TME and the abundance of tumour-infiltrating immune cells (TICs) were calculated by the ESTIMATE and CIBERSORT algorithms, respectively. The differentially expressed microRNAs (DEMs) between different StromalScore and ImmuneScore groups were screened out by the edgeR package. Bioinformatics analysis was performed to screen out important DEMs and explore their functional effect.
Results
Our results revealed that a low StromalScore, ImmuneScore and ESTIMATEScore led to poor prognosis of LUAD. Then, 62 DEMs were screened out as downregulated in both the high StromalScore and ImmuneScore groups. Among these DEMs, elevated expression levels of miR-873, miR-105-2 and miR-516a-2 significantly shortened the survival time of LUAD patients. Subsequent analysis revealed that the expression levels of miR-873 and miR-105-2 were increased significantly in tumour tissues. The expression patterns of these 2 microRNAs were confirmed by GSE102286, implying the important roles of these 2 microRNAs in LUAD. Further analysis showed that miR-873 and miR-105-2 were mainly involved in immune-related pathways and that high expression levels of miR-873 and miR-105-2 decreased the abundance of monocytes and resting dendritic cells in the TME.
Conclusion
Although further exploration is still needed, our results revealed that miR-873 and miR-105-2 were closely related to the TME and affected the prognosis of LUAD by altering the abundance of TICs.
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