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Deep sequencing of exosomal and cellular miRNAs in MDA-MB-231 and MCF-10A cells

ABSTRACT: To identify the miRNAs that are differentially expressed and secreted between the MDA-MB-231 metastatic breast cancer cells and the MCF-10A non-cancerous human mammary epithelial cells, we profiled the cellular and exosomal small RNAs (between 17 and 52 nt) isolated from these two cell lines by Solexa deep sequencing. MiRNAs that are significantly different between the two cell lines are identified.

ORGANISM(S): Homo sapiens

PROVIDER: GSE50429 | GEO | 2013/09/01

SECONDARY ACCESSION(S): PRJNA217805

REPOSITORIES: GEO

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Project description:Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype that promotes higher risk of metastasis and cancer reoccurrence, subsequently reduces survival rate of cancer patients. Cisplatin is one of the potential anticancer drugs for treating TNBC. However, occurrence of cisplatin resistance still remains as one of the challenges to fully eradicate TNBC. Since presence of cancer stem cells (CSCs) often known as one of the contributors of drug resistance, investigation has been conducted, suggesting sorted CSC-like subpopulation to be more resistant to cisplatin as compared to parental cells, alongside with higher self-renewability. On the other hand, plethora evidences showed the transmission of exosomal-miRNAs are capable of promoting drug resistance in breast cancers. In this study, we aim to elucidate the differential expression of exosomal-microRNAs profile and reveal the potential target genes in correlation to cisplatin resistance associated with CSC-like subpopulation by using TNBC cell line (MDA-MB-231). Utilizing next generation sequencing and Nanostring techniques, cisplatin-induced dysregulation of exosomal-miRNAs were evaluated in maximal for CSC-like subpopulation as compared to parental cells. Intriguingly, cisplatin induced a relatively oncogenic exosomal-miRNAs profile derived from treated CSC-like subpopulation as compared to treated parental cells, which may correlate to enhancement of drug resistance and maintenance of CSCs. Among the detected exosomal-miRNA profile in treated CSC-like subpopulation, unique clusters of miRNAs namely miR-221-3p, miR-196a-5p, miR-17-5p and miR-126-3p were predicted to target on six genes (ATXN1, LATS1, GSK3β, ITGA6, JAG1 and MYC), aligned with previous finding which demonstrated dysregulation of these genes in treated CSC-like subpopulation. Our results highlight the potential correlation of exosomal-miRNAs and their target genes as well as novel perspectives of the corresponding pathways that may be essential to contribute to the attenuated cytotoxicity of cisplatin in CSC-like subpopulation.

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Deep sequencing of exosomal and cellular miRNAs in MDA-MB-231 and MCF-10A cells

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