Dataset Information

RBM8A Depletion Decreases the Cisplatin Resistance and Represses the Proliferation and Metastasis of Breast Cancer Cells via AKT/mTOR Pathway.

ABSTRACT:

Background

Breast cancer (BC) is the most prevalent malignancy in women. This study is aimed to explore the role and regulatory mechanism of RNA-binding motif protein 8A (RBM8A) in BC.

Methods

We detected the expression of RBM8A in BC tissues and cell lines (MCF-7, MDA-MB-231, and MDA-MB-436), and explored the correlation of RBM8A expression with clinicopathological features in patients. The function of RBM8A deficiency in MCF-7 and MDA-MB-231 cells was determined using MTT, wound healing, and transwell assay. The effect of RBM8A suppression on the cisplatin (DDP) resistance in MCF-7 and MDA-MB-231 cells was also evaluated. Besides, western blotting was used to examine AKT/mTOR pathway-related proteins. The mouse model was constructed to confirm the effect of RBM8A on tumor growth.

Results

The expression of RBM8A was elevated in BC tissues and cell lines. RBM8A silencing restrained the malignant behaviors of MCF-7 and MDA-MB-231 cells, including viability, migration, and invasion, while promoting apoptosis. Silencing of RBM8A overcame resistance to DDP in MCF-7 and MDA-MB-231 cells. Furthermore, RBM8A suppression restrained the activation of the AKT/mTOR pathway in both MCF-7 and MDA-MB-231 cells. Feedback experiments revealed that SC79 treatment reversed the reduction effects of RBM8A knockdown on viability, DDP resistance, migration, and invasion of MDA-MB-231 cells. Moreover, the silencing of RBM8A inhibited the growth of tumor xenograft in vivo.

Conclusions

RBM8A knockdown may reduce DDP resistance in BC to repress the development of BC via the AKT/mTOR pathway, suggesting that RBM8A may serve as a new therapeutic target in BC.

SUBMITTER: Song T

PROVIDER: S-EPMC9441397 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

RBM8A Depletion Decreases the Cisplatin Resistance and Represses the Proliferation and Metastasis of Breast Cancer Cells via AKT/mTOR Pathway.

Song Tao T Zhang Huazhou H

The breast journal 20220828

<h4>Background</h4>Breast cancer (BC) is the most prevalent malignancy in women. This study is aimed to explore the role and regulatory mechanism of RNA-binding motif protein 8A (RBM8A) in BC.<h4>Methods</h4>We detected the expression of RBM8A in BC tissues and cell lines (MCF-7, MDA-MB-231, and MDA-MB-436), and explored the correlation of RBM8A expression with clinicopathological features in patients. The function of RBM8A deficiency in MCF-7 and MDA-MB-231 cells was determined using MTT, wound ...[more]

PMID: 36105365

Similar Datasets

Project description:BackgroundUbiquitin-conjugating enzyme E2C (UBE2C) has been shown to be associated with the occurrence of various cancers and involved in many tumorigenic processes. This study aimed to investigate the specific molecular mechanism through which UBE2C affects breast cancer (BC) proliferation.MethodsBC-related datasets were screened according to filter criteria in the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. Then differentially expressed genes (DEGs) were identified using Venn diagram analysis. By using DEGs, we conducted the following analyses including Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI), and survival analysis, and then validated the function of the hub gene UBE2C using quantitative reverse transcription-polymerase chain reaction (RT-qPCR), cell counting kit-8 (CCK-8) assay, transwell assay, and Western blot assay.ResultsIn total, 151 DEGs were identified from the GEO and TCGA databases. The results of GO analysis demonstrated that the DEGs were significantly enriched with mitotic nuclear division, lipid droplet, and organic acid-binding. KEGG analysis showed that the peroxisome proliferators-activated receptor (PPAR) signaling pathway, regulation of lipolysis in adipocytes, and proximal tubule bicarbonate reclamation were significantly enriched in the signal transduction pathway category. The top three hub genes that resulted from the PPI network were FOXM1, UBE2C, and CDKN3. The results of survival analysis showed a close relationship between UBE2C and BC. The results of CCK-8 and transwell assays suggested that the proliferation and invasion of UBE2C knockdown cells were significantly inhibited (P < 0.050). The results of Western blot assay showed that the level of phosphorylated phosphatase and tensin homology deleted on chromosome 10 (p-PTEN) was obviously increased (P < 0.050), whereas the levels of phosphorylated protein kinase B (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), and hypoxia-inducible factor-1 alpha (HIF-1α) were dramatically decreased (P < 0.050) in the UBE2C knockdown cell.ConclusionUBE2C can promote BC proliferation by activating the AKT/mTOR signaling pathway.

Dataset Information

RBM8A Depletion Decreases the Cisplatin Resistance and Represses the Proliferation and Metastasis of Breast Cancer Cells via AKT/mTOR Pathway.

Background

Methods

Results

Conclusions

Publications

RBM8A Depletion Decreases the Cisplatin Resistance and Represses the Proliferation and Metastasis of Breast Cancer Cells via AKT/mTOR Pathway.

Similar Datasets

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