The hsa-miR-1246 is overexpressed in Spheroids-derived cancer stem cells from tumor cell lines

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Abstract

Tumors consist of various cell types, including a small population of cancer stem cells (CSCs), which are linked to metastasis, drug resistance, and recurrence. Maintaining the CSC phenotype requires regulation of molecules, including miRNAs; they are small non-coding RNAs involved in processes such as proliferation, differentiation, invasion, and apoptosis. However, miRNAs involved in CSC generation and maintenance remain largely unidentified. In this study, we aimed to identify miRNAs associated with CSC populations by studying the miRNA profiles in Spheroids-Derived cancer stem cells (SDCSCs) from different cancer cell lines. Firstly, we used small RNA sequencing by Illumina to identify differentially expressed miRNAs from SDCSCs compared with adherent cells from lung cancer cell line. Next, we conducted a meta-analysis to integrate expression data from studies performed under same conditions from several tumor cell lines such as ovarium, breast, colorectal cancer cell lines. We reanalyzed microarrays and RNA sequencing data and for integration we employed the Robust Rank Aggregation approach. We identified only one upregulated miRNA, the hsa-miR-1246. Bioinformatics analysis revealed that hsa-miR-1246 interacts with cyclins, GSK3B, and other experimentally validated targets, which were related to the cell cycle and the regulation of transcription from RNA polymerase II. These findings suggest that hsa-miR-1246 may promote CSC generation and maintenance by regulating these processes. Our study enhances the understanding of miRNA involvement in CSCs and identifies potential targets, addressing both undifferentiated tumor cells and the more aggressive CSC population. Further validation using vivo models and functional knockdowns is needed to confirm these results in CSC biology,

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