Role of regulatory miRNAs of the Wnt/ β-catenin signaling pathway in tumorigenesis of breast cancer

Rahmani, Farzad; Tabrizi, Ayda Tadayyon; Hashemian, Pedram; Alijannejad, Sajede; Rahdar, Hossein Ali; Ferns, Gordon A.; Hassanian, Seyed Mahdi; Shahidsales, Soodabeh

doi:10.1016/j.gene.2020.144892

Cited by 27 publications

(14 citation statements)

References 66 publications

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“…Accumulating evidence has shown that the Wnt/β-catenin pathway not only determines mammary development, but also regulates self-renewal, tumorigenesis and differentiation of CSCs in various cancers including breast cancer, lung cancer, and prostate cancer. β-catenin is the core target of this signaling, and its nuclear accumulation and translocation leads to transcription of downstream genes such as ABCG2 , HMGB1 , cyclin D1 , c-myc , and Axin2 , which are strongly correlated to cancer chemosensitivity ( Cheng et al, 2019 ; Rahmani et al, 2020 ; Yousefnia et al, 2020 ). Upon the activation of β-catenin, the complex composed of Axin and glycogen synthase kinase-3β (GSK-3β) prevents the phosphorylation and degradation of β-catenin, increases the concentration of β-catenin in cytoplasm, and then transfers into the nucleus to interact with T cell transcription factor/lymphoid enhancer factor to activate the Wnt1/β-catenin signal pathway, and finally start the transcription of downstream target genes such as cyclin D1 and c-myc , resulting in abnormal proliferation of CSCs and tumor drug resistance ( Maiese, 2014 ; Schuijers et al, 2014 ; Ashouri et al, 2016 ; Hassanian et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Autophagy Blockade by Ai Du Qing Formula Promotes Chemosensitivity of Breast Cancer Stem Cells Via GRP78/β-Catenin/ABCG2 Axis

et al. 2021

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Accumulating evidence suggests that the root of drug chemoresistance in breast cancer is tightly associated with subpopulations of cancer stem cells (CSCs), whose activation is largely dependent on taxol-promoting autophagy. Our pilot study identified GRP78 as a specific marker for chemoresistance potential of breast CSCs by regulating Wnt/β-catenin signaling. Ai Du Qing (ADQ) is a traditional Chinese medicine formula that has been utilized in the treatment cancer, particularly during the consolidation phase. In the present study, we investigated the regulatory effects and molecular mechanisms of ADQ in promoting autophagy-related breast cancer chemosensitivity. ADQ with taxol decreasing the cell proliferation and colony formation of breast cancer cells, which was accompanied by suppressed breast CSC ratio, limited self-renewal capability, as well as attenuated multi-differentiation. Furthermore, autophagy in ADQ-treated breast CSCs was blocked by taxol via regulation of β-catenin/ABCG2 signaling. We also validated that autophagy suppression and chemosensitizing activity of this formula was GRP78-dependent. In addition, GRP78 overexpression promoted autophagy-inducing chemoresistance in breast cancer cells by stabilizing β-catenin, while ADQ treatment downregulated GRP78, activated the Akt/GSK3β-mediated proteasome degradation of β-catenin via ubiquitination activation, and consequently attenuated the chemoresistance-promoted effect of GRP78. In addition, both mouse breast cancer xenograft and zebrafish xenotransplantation models demonstrated that ADQ inhibited mammary tumor growth, and the breast CSC subpopulation showed obscure adverse effects. Collectively, this study not only reveals the chemosensitizating mechanism of ADQ in breast CSCs, but also highlights the importance of GRP78 in mediating autophagy-promoting drug resistance via β-catenin/ABCG2 signaling.

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Section: Introductionmentioning

confidence: 99%

Autophagy Blockade by Ai Du Qing Formula Promotes Chemosensitivity of Breast Cancer Stem Cells Via GRP78/β-Catenin/ABCG2 Axis

et al. 2021

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“…The Wnt/ β -catenin pathway has been reported to regulate tumorigenesis and progression of BC [ 31 – 33 ]. Li et al showed that TRIM63, a novel oncogene, promotes BC cell proliferation and migration via activating the Wnt/ β -catenin signaling pathway [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Circ-DONSON Knockdown Inhibits Cell Proliferation and Radioresistance of Breast Cancer Cells via Regulating SOX4

Zhu

2021

Journal of Oncology

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Background. Circular RNAs have been validated as critical regulators in the development of breast cancer (BC). Circ-DONSON is involved in the progression of glioma and gastric cancer. However, the biological role of circ-DONSON in BC remains unclear, and the aim of this study was to explore the biological role of circ-DONSON in BC. Methods. Human tissue samples and BC cell lines were collected in this study. siRNAs against circ-DONSON were transfected into BC cell lines for silencing of circ-DONSON. Quantitative real-time PCR was used to test the circ-DONSON expression. Cell counting kit-8 (CCK-8), 5-bromo-2′ deoxyuridine enzyme-linked immunosorbent assay (BrdU-ELISA), colony formation, and caspase-3 activity assays were used to assess cell proliferation, cell survival, and cell viability. Western blotting analysis was used to detect the protein expression levels. Results. Our findings showed that circ-DONSON showed high expression in BC tissues and cell lines. CCK-8 and BrdU-ELISA assays showed that circ-DONSON knockdown inhibited BC cell proliferation. Moreover, cell survival, cell viability, and caspase-3 activity assays showed that circ-DONSON knockdown reduced the radioresistance of BC cells. Mechanistically, circ-DONSON regulated BC cell proliferation and radioresistance via SRY-box transcription factor 4 (SOX4). SOX4 overexpression significantly rescued the effect of circ-DONSON knockdown on BC cell proliferation and radioresistance. Moreover, circ-DONSON activated the Wnt/β-catenin pathway in BC cells via SOX4. Conclusion. Our study concluded that circ-DONSON knockdown hindered cell proliferation and radioresistance through the SOX4/Wnt/β-catenin pathway in BC.

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“…Studies have been reported that upregulation of Wnt/β-catenin was shown to be one of the mechanisms to resist PI3k inhibitors. In addition, the use of β-catenin inhibitors sensitizes breast cancer cells to PI3K inhibitors [353].…”

Section: Mapk/erk Signaling Pathwaymentioning

confidence: 99%

The Anticancer Effects of Flavonoids through miRNAs Modulations in Triple-Negative Breast Cancer

et al. 2021

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Triple- negative breast cancer (TNBC) incidence rate has regularly risen over the last decades and is expected to increase in the future. Finding novel treatment options with minimum or no toxicity is of great importance in treating or preventing TNBC. Flavonoids are new attractive molecules that might fulfill this promising therapeutic option. Flavonoids have shown many biological activities, including antioxidant, anti-inflammatory, and anticancer effects. In addition to their anticancer effects by arresting the cell cycle, inducing apoptosis, and suppressing cancer cell proliferation, flavonoids can modulate non-coding microRNAs (miRNAs) function. Several preclinical and epidemiological studies indicate the possible therapeutic potential of these compounds. Flavonoids display a unique ability to change miRNAs’ levels via different mechanisms, either by suppressing oncogenic miRNAs or activating oncosuppressor miRNAs or affecting transcriptional, epigenetic miRNA processing in TNBC. Flavonoids are not only involved in the regulation of miRNA-mediated cancer initiation, growth, proliferation, differentiation, invasion, metastasis, and epithelial-to-mesenchymal transition (EMT), but also control miRNAs-mediated biological processes that significantly impact TNBC, such as cell cycle, immune system, mitochondrial dysregulation, modulating signaling pathways, inflammation, and angiogenesis. In this review, we highlighted the role of miRNAs in TNBC cancer progression and the effect of flavonoids on miRNA regulation, emphasizing their anticipated role in the prevention and treatment of TNBC.

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Role of regulatory miRNAs of the Wnt/ β-catenin signaling pathway in tumorigenesis of breast cancer

Cited by 27 publications

References 66 publications

Autophagy Blockade by Ai Du Qing Formula Promotes Chemosensitivity of Breast Cancer Stem Cells Via GRP78/β-Catenin/ABCG2 Axis

Autophagy Blockade by Ai Du Qing Formula Promotes Chemosensitivity of Breast Cancer Stem Cells Via GRP78/β-Catenin/ABCG2 Axis

Circ-DONSON Knockdown Inhibits Cell Proliferation and Radioresistance of Breast Cancer Cells via Regulating SOX4

The Anticancer Effects of Flavonoids through miRNAs Modulations in Triple-Negative Breast Cancer

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