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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

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

PROVIDER: PRJNA994060 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25247949.fastq.gz	Fastqsanger.gz
	SRR25247950.fastq.gz	Fastqsanger.gz

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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

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

Project description:Due to alternative processing pathway and post-transcriptional modifications, precursor miRNAs maturate into various sequence isoforms (isomiRs). These sequence variations may result in the changes of the miRNA seed site, target genes, involvement in signaling pathways and thus function. It is important to mention that knowledge about the targets of isomiR is still poor. To date, isomiR research has only been performed in melanoma, breast, and gastric cancer, but there are no experimental studies conducted in colorectal cancer. Here, we aimed to evaluate the putative targets and functional role in vitro of miR-1246 and its two 5’ isoforms (ISO-miR-1246_a and ISO-miR-1246_G). To our best knowledge, this is the first study showing the important role of 5’isoforms of miR-1246 in colorectal carcinogenesis, while acting on different targetomes and being involved in distinct signaling pathways.

2024-02-26 | GSE237144 | GEO

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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5'-Isoforms of miR-1246 Have Distinct Targets and Stronger Functional Impact Compared with Canonical miR-1246 in Colorectal Cancer Cells In Vitro.

Project description:Colorectal cancer (CRC) is a multifactorial disease involving genetic and epigenetic factors, such as miRNAs. Sequencing-based studies have revealed that miRNAs have many isoforms (isomiRs) with modifications at the 3'- and 5'-ends or in the middle, resulting in distinct targetomes and, consequently, functions. In the present study, we aimed to evaluate the putative targets and functional role of miR-1246 and its two 5'-isoforms (ISO-miR-1246_a and ISO-miR-1246_G) in vitro. Commercial Caco-2 cells of CRC origin were analyzed for the expression of WT-miR-1246 and its 5'-isoforms using small RNA sequencing data, and the overabundance of the two miR-1246 isoforms was determined in cells. The transcriptome analysis of Caco-2 cells transfected with WT-miR-1246, ISO-miR-1246_G, and ISO-miR-1246_a indicated the minor overlap of the targetomes between the studied miRNA isoforms. Consequently, an enrichment analysis showed the involvement of the potential targets of the miR-1246 isoforms in distinct signaling pathways. Cancer-related pathways were predominantly more enriched in dysregulated genes in ISO-miR-1246_G and ISO-miR-1246_a, whereas cell cycle pathways were more enriched in WT-miR-1246. The functional analysis of WT-miR-1246 and its two 5'-isoforms revealed that the inhibition of any of these molecules had a tumor-suppressive role (reduced cell viability and migration and promotion of early cell apoptosis) in CRC cells. However, the 5'-isoforms had a stronger effect on viability compared with WT-miR-1246. To conclude, this research shows that WT-miR-1246 and its two 5'-isoforms have different targetomes and are involved in distinct signaling pathways but collectively play an important role in CRC pathogenesis.

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

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

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

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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