circ_103809 promotes breast cancer progression by regulating the PI3K/AKT signaling pathway

Chemo-resistance and metastatic disease development are the most common causes of breast cancer recurrence and death. Thidiazuron (TDZ) is a plant growth regulator, its biological role on human and animals has not been yet clarified. In the present study, we investigated the anticancer activity of this plant phytohormone on the drug resistant-triple negative breast cancer MDA-MB-231 cell line. Treatment of the breast cancer cells with TDZ (1-50 μM) caused more stressful environment and induced a significant increase in percentages of active caspases positive cells. In addition, TDZ treatment (5 and 10 μM) significantly attenuated the migration and the invasion activities of these highly metastatic cancer cells. Mechanistically, TDZ reducesd cancer progression and invasive activity through targeting miR-202-5p, which stimulatesd the expression of the phosphatase and tensin homolog (PTEN), the tumor suppressor that downregulates PI3K/AKT signaling pathway. In the meantime, TDZ treatment statistically upregulatesd the suppressor of breast cancer proliferation, miRNA-132 that is also implicated in dysregulating the TEN-AKT/the nuclear factor NFκB signaling pathway. Interestingly, our molecular docking analysis revealed potential non-covalent interaction between TDZ with AKT, PTEN and PI3K. These findings suggest that TDZ may suppresses breast cancer metastasis through targeting miRNA-132, miR-202-5p/PTEN and PI3K/AKT downstream molecules.

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Comprehensive Combined Proteomics and Genomics Analysis Identifies Prognostic Related Transcription Factors in Breast Cancer and Explores the Role of DMAP1 in Breast Cancer

Journal of Personalized Medicine ◽

10.3390/jpm11111068 ◽

2021 ◽

Vol 11 (11) ◽

pp. 1068

Author(s):

Xuan Li ◽

Hefen Sun ◽

Yifeng Hou ◽

Wei Jin

Keyword(s):

Breast Cancer ◽

Transcription Factors ◽

Signaling Pathway ◽

Cancer Progression ◽

Immune Cell ◽

Akt Signaling ◽

High Expression ◽

Akt Signaling Pathway ◽

Normal Tissues

Transcription factors (TFs) are important for regulating gene transcription and are the hallmark of many cancers. The identification of breast cancer TFs will help in developing new diagnostic and individualized cancer treatment tools. In this study, we used quantitative proteomic analyses of nuclear proteins and massive transcriptome data to identify enriched potential TFs and explore the possible role of the transcription factor DMAP1 in breast cancer. We identified 13 prognostic-related TFs and constructed their regulated genes, alternative splicing (AS) events, and splicing factor (SF) regulation networks. DMAP1 was reported less in breast cancer. The expression of DMAP1 decreased in breast cancer tumors compared with normal tissues. The poor prognosis of patients with low DMAP1 expression may relate to the activated PI3K/Akt signaling pathway, as well as other cancer-relevant pathways. This may be due to the low methylation and high expression of these pathway genes and the fact that such patients show more sensitivity to some PI3K/Akt signaling pathway inhibitors. The high expression of DMAP1 was correlated with low immune cell infiltration, and the response to immune checkpoint inhibitor treatment in patients with high DMAP1 expression was low. Our study identifies some transcription factors that are significant for breast cancer progression, which can be used as potential personalized prognostic markers in the future.

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Hypermethylation of DLG3 Promoter Upregulates RAC1 and Activates the PI3K/AKT Signaling Pathway to Promote Breast Cancer Progression

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/8428130 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Bingbing Liu ◽

Yanning Xu ◽

Lin Zhang ◽

Xue Yang ◽

Ling Chen ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Signaling Pathway ◽

Cancer Progression ◽

Epithelial Mesenchymal Transition ◽

Biological Activities ◽

Akt Signaling ◽

Akt Pathway ◽

Akt Signaling Pathway ◽

Mesenchymal Transition

Objective. This investigation aimed to figure out the relation between discs large homolog 3 (DLG3) expression and the progression and prognosis of breast cancer (BC). Methods. qRT-PCR was utilized for confirming DLG3 expression and RAC1 mRNA expression in BC tissues and cells. Subsequently, after overexpression or interference of DLG3, the changes of the biological activities of BC cells, including cell proliferation, migration, invasion, and apoptosis, were detected through CCK-8, colony formation assay, wound healing assay, transwell assay, and flow cytometry, respectively. Furthermore, western blotting was utilized to measure the protein expression of DLG3 and RAC1, as well as related proteins of epithelial-mesenchymal transition (EMT) and the PI3K/AKT signaling pathway. Results. At both cellular and tissue level in BC, DLG3 was downregulated and methylation level was upregulated; RAC1 showed an opposite change and was of a negative correlation with DLG3. In MCF-7 and HCC1937, we found that the upregulation of DLG3 could inhibit RAC1 expression as well as cell proliferation, invasion, migration, and EMT, while promoting apoptosis. Also, DLG3 inhibited the activation of the P13K/AKT pathway. Conclusion. Hypermethylation of DLG3 promoter upregulates RAC1 and activates the PI3K/AKT pathway, thus promoting BC progression. This conclusion provides ideas and experimental basis for improving and treating BC patients.

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