Dataset Information

MicroRNA expression profiles in extracellular vesicles and intracellular of AURKA inhibitor-induced senescent neuroblastoma cells.

ABSTRACT:

Background

Therapy-induced senescence plays an important role in the clinical treatment of tumors, which is positively correlated with the treatment response. However, senescent cells reshape tumor microenvironment and increase the risk of cancer recurrence. Regarded as hormones to regulate cell-to-cell communication, microRNA (miRNA) is highly sensitive to environmental stress. To understand the response of tumor cells to chemotherapeutic drugs, miRNAs in chemotherapy-induced senescent cells and their secreted extracellular vehicles (EVs) were detected and the miRNA profiles were analyzed, hoping to provide some thoughts for the evaluation of chemotherapy effect in clinical tumor treatment.

Methods

Neuroblastoma cell line IMR32 was treated with low concentration of aurora kinase A (AURKA) inhibitor MLN8237 to establish a cell senescence model. RNAs were extracted from senescent cells and extracellular vesicles, and miRNA spectrum was investigated by small RNA deep sequencing.

Results

Thirteen miRNAs including miR-378b and miR-206 were significantly increased, whereas 32 miRNAs including miR-205-5p, miR-378d, and miR-378f were significantly decreased in the senescence cell group. In senescent cells secreted extracellular vesicles, there were 48 of up-regulated miRNAs including miR-205-5p and 9 of down-regulated miRNAs. Bioinformatics analysis revealed that these differentially expressed miRNAs in senescent cells may potentially regulate many common target genes which belong to the metabolic signaling pathway and transcriptional misregulation in cancer.

Conclusions

The expression profiles of miRNA in senescent neuroblastoma cells and extracellular vesicles were altered, and the differentially expressed miRNAs were mostly involved in cellular metabolic pathways. The information decryption can provide reference for clinical interpretation of the phenomenon of therapy-induced senescence.

SUBMITTER: Zhou X

PROVIDER: S-EPMC9459525 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

MicroRNA expression profiles in extracellular vesicles and intracellular of AURKA inhibitor-induced senescent neuroblastoma cells.

Zhou Xuefeng X Zhou Qi Q Zhou Di D Li Fen F Zhang Chunyan C Yang Yan Y

Translational cancer research 20220801 8

<h4>Background</h4>Therapy-induced senescence plays an important role in the clinical treatment of tumors, which is positively correlated with the treatment response. However, senescent cells reshape tumor microenvironment and increase the risk of cancer recurrence. Regarded as hormones to regulate cell-to-cell communication, microRNA (miRNA) is highly sensitive to environmental stress. To understand the response of tumor cells to chemotherapeutic drugs, miRNAs in chemotherapy-induced senescent ...[more]

PMID: 36093520

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Project description:Triple negative breast cancer (TNBC) is an aggressive subtype with relatively poor clinical outcomes and limited treatment options. Chemotherapy, while killing cancer cells, can result in the generation of highly chemoresistant therapeutic induced senescent (TIS) cells that potentially form stem cell niches resulting in metastases. Intriguingly, senescent cells release significantly more extracellular vesicles (EVs) than non-senescent cells. Our aim was to profile EVs harvested from TIS TNBC cells compared with control cells to identify a potential mechanism by which TIS TNBC cells maintain survival in the face of chemotherapy. TIS was induced and confirmed in Cal51 TNBC cells using the chemotherapeutic paclitaxel (PTX) (Taxol). Mass spectrometry (MS) analysis of EVs harvested from TIS compared with control Cal51 cells was performed using Ingenuity Pathway Analysis and InnateDB programs. We demonstrate that TIS Cal51 cells treated with 75 nM PTX for 7 days became senescent (senescence-associated β-galactosidase (SA-β-Gal) positive, Ki67-negative, increased p21 and p16, G2/M cell cycle arrest) and released significantly more EVs (P=0.0002) and exosomes (P=0.0007) than non-senescent control cells. Moreover, TIS cells displayed an increased expression of the multidrug resistance protein 1/p-glycoprotein. MS analysis demonstrated that EVs derived from senescent Cal51 cells contained 142 proteins with a significant increased fold change compared with control EVs. Key proteins included ATPases, annexins, tubulins, integrins, Rabs and insoluble senescence-associated secretory phenotype (SASP) factors. A fluorescent analogue of PTX (Flutax-2) allowed appreciation of the removal of chemotherapy in EVs from senescent cells. Treatment of TIS cells with the exosome biogenesis inhibitor GW4869 resulted in reduced SA-β-Gal staining (P=0.04). In summary, this study demonstrates that TIS cells release significantly more EVs compared with control cells, containing chemotherapy and key proteins involved in cell proliferation, ATP depletion, apoptosis and the SASP. These findings may partially explain why cancer senescent cells remain viable despite chemotherapeutic challenge.

Dataset Information

MicroRNA expression profiles in extracellular vesicles and intracellular of AURKA inhibitor-induced senescent neuroblastoma cells.

Background

Methods

Results

Conclusions

Publications

MicroRNA expression profiles in extracellular vesicles and intracellular of AURKA inhibitor-induced senescent neuroblastoma cells.

Similar Datasets

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