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Tumor-initiating cell-specific miR-1246 and miR-1290 converge to promote non-small cell lung cancer progression [Illumina]

ABSTRACT: The tumor-initiating cell (TIC) model accounts for the phenotypic and functional heterogeneity among cancer cells found within human cancers. MicroRNAs (miRNAs) are key regulatory molecules frequently aberrantly expressed in tumors, and may play important roles in contributing towards tumor heterogeneity and TIC behavior. More recent efforts have focused on miRNAs for diagnosis and as targets for novel therapies. In this study, we identified the miRNAs, miR-1246 and miR-1290, which are crucial for the function of TICs, thereby driving cancer progression in human non-small cell lung cancer (NSCLC). These miRNAs are restricted to patient-derived tumorspheres and CD166+ primary tumor cells, both enriched for TICs. Loss of either miRNA impacted the tumorigenic potential of TICs and their ability to metastasize. Interestingly, longitudinal analyses of serum miR-1246 and miR-1290 levels correlated circulating levels of either miRNA to the clinical response seen in lung cancer patients to epidermal growth factor receptor (EGFR) tyrosine kinase inhibition, chemotherapy and radiotherapy. Functionally, direct inhibition of miR-1246 or miR-1290 with locked nucleic acid (LNA) administered systemically, could arrest the growth of established patient-derived tumors xenografted in immunocompromised mice, thus indicating these miRNAs are clinically useful as biomarkers for tracking disease progression and as therapeutic targets.

ORGANISM(S): Homo sapiens

PROVIDER: GSE69630 | GEO | 2015/11/30

SECONDARY ACCESSION(S): PRJNA286043

REPOSITORIES: GEO

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Tumor-initiating cell-specific miR-1246 and miR-1290 converge to promote non-small cell lung cancer progression [Agilent]

Project description:The tumor-initiating cell (TIC) model accounts for the phenotypic and functional heterogeneity among cancer cells found within human cancers. MicroRNAs (miRNAs) are key regulatory molecules frequently aberrantly expressed in tumors, and may play important roles in contributing towards tumor heterogeneity and TIC behavior. More recent efforts have focused on miRNAs for diagnosis and as targets for novel therapies. In this study, we identified the miRNAs, miR-1246 and miR-1290, which are crucial for the function of TICs, thereby driving cancer progression in human non-small cell lung cancer (NSCLC). These miRNAs are restricted to patient-derived tumorspheres and CD166+ primary tumor cells, both enriched for TICs. Loss of either miRNA impacted the tumorigenic potential of TICs and their ability to metastasize. Interestingly, longitudinal analyses of serum miR-1246 and miR-1290 levels correlated circulating levels of either miRNA to the clinical response seen in lung cancer patients to epidermal growth factor receptor (EGFR) tyrosine kinase inhibition, chemotherapy and radiotherapy. Functionally, direct inhibition of miR-1246 or miR-1290 with locked nucleic acid (LNA) administered systemically, could arrest the growth of established patient-derived tumors xenografted in immunocompromised mice, thus indicating these miRNAs are clinically useful as biomarkers for tracking disease progression and as therapeutic targets.

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Exosomal miR-1290 and miR-375 as prognostic markers in castrate resistant prostate cancer

Project description:Extracellular microRNAs (miRNAs) embedded in circulating exosomes may serves as prognostic biomarkers in cancer. This study was performed to identify and evaluate plasma exosomal miRNAs for prognostication in castration resistant prostate cancer (CRPC). RNA sequencing was performed to identify candidate exosomal miRNAs associated with overall survival in a screening cohort of 23 CRPC patients. Candidate miRNAs were further evaluated for prognosis using qRT-PCR in a follow-up cohort of 100 patients. Cox regression and Kaplan–Meier survival curve analysis were used to evaluate prognostic value of miRNA candidates with and without incorporation of clinical prognostic factors (age, Gleason score and time from androgen deprivation therapy to clinical progression). In the screening cohort, we obtained ~6.80 million mappable RNA reads per patient. Of those with normalized read counts ? 5, 43% were mapped to miRNAs for a total of 375 known and 57 novel miRNAs. Cox regression analysis identified an association of miR-1290, -1246, and -375 with overall survival (FDR<0.1). Of those, higher levels of miR-1290 and -375 were verified to be significantly associated with poor overall survival (p<0.004) in the follow-up cohort. The miR-1290/-375-based prediction model showed better performance with time-dependent area under the curve (AUC) =72% compared to clinical variable-based model with AUC=65%. Plasma exosomal miR-1290 and miR-375 are promising prognostic biomarkers for CRPC patients. Prospective validation is needed for further development of these candidate miRNAs.

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Tumor-initiating cell-specific miR-1246 and miR-1290 converge to promote non-small cell lung cancer progression

Project description:Tumor-initiating cell-specific miR-1246 and miR-1290 converge to promote non-small cell lung cancer progression

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5’ isoforms of miR-1246 have distinct targets and stronger functions compared to canonical miR-1246 in colorectal cancer cells in vitro

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Exosomal microRNA, miR-1246, induces cell motility and invasion through the regulation of DENND2D in oral squamous cell carcinoma

2016-08-15 | GSE83981 | GEO

Exosomal microRNA, miR-1246, induces cell motility and invasion through the regulation of DENND2D in oral squamous cell carcinoma

Project description:To Identify of metastasis-related genes and metastasis-related miRNA in oral squamous cell carcinoma by miRNA profiling of HOC313-Parent, HOC313-LM and their respective exosomes carried out. As a result, miR-342-3p and -1246 were found candidate oncogenic miRNAs. To further identify the target genes of miR-1246 and miR-342-3p, we performed gene expression array analysis with HOC313-LM and HOC313-Parent (HOC313-P) transfected NT, miR-342-3p and miR-1246. Moreover, to identify tumor suppressor genes, gene expression profiles of each of transfected cells and HOC313-LM cells were analyzed by in silico analyses. As a result, DENND2D emerged as the possible target of miRN-1246. Extraction of difference of miRNA expression level between whole cell and exosomes of HOC313-Parent and HOC313-LM. Also, extraction of difference of gene expression level between high-metastatic subline (HOC313-LM) and low-metastatic subline (HOC313-P). Moreover the miRNA expression profiles and gene expression profiles were analyzed by in silico analyses.

2016-08-15 | E-GEOD-83981 | biostudies-arrayexpress

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