MicroRNA‑454‑5p promotes breast cancer progression by inducing epithelial‑mesenchymal transition via targeting the FoxJ2/E‑cadherin axis

Wang, Cuiping; Yu, Yong-Zheng; Zhao, Hui; Xie, Lei; Wang, Qitang; Wang, Ye; Mu, Qiang

doi:10.3892/or.2021.8078

Cited by 7 publications

(3 citation statements)

References 47 publications

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“…[ 33 ] Previous studies have reported a positive association between FOXJ2 and the pathophysiology of cancers as well as autoimmune disorders. [ 34 , 35 , 36 ] In this study, we identified the upregulation of FOXJ2 in APS for the first time, demonstrating the important role of FOXJ2 in monocytes for regulating APS pathogenesis. Considering the essential roles of activated ECs and platelets in APS, FOXJ2 might also epigenetically regulate the function of ECs and platelets during the progression of APS, which is worth investigating.…”

Section: Discussionmentioning

confidence: 70%

H3K4me3‐Mediated FOXJ2/SLAMF8 Axis Aggravates Thrombosis and Inflammation in β2GPI/Anti‐β2GPI‐Treated Monocytes

Tan,

Qiao,

Yang

et al. 2024

Advanced Science

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Antiphospholipid syndrome (APS) is characterized by thrombus formation, poor pregnancy outcomes, and a proinflammatory response. H3K4me3‐related monocytes activation are key regulators of APS pathogenesis. Therefore, H3K4me3 CUT&Tag and ATAC‐seq are performed to examine the epigenetic profiles. The results indicate that the H3K4me3 signal and chromatin accessibility at the FOXJ2 promoter are enhanced in an in vitro monocyte model by stimulation with β2GPI/anti‐β2GPI, which mimics APS, and decreases after OICR‐9429 administration. Furthermore, FOXJ2 is highly expressed in patients with primary APS (PAPS) and is the highest in patients with triple‐positive antiphospholipid antibodies (aPLs). Mechanistically, FOXJ2 directly binds to the SLAMF8 promoter and activates SLAMF8 transcription. SLAMF8 further interacts with TREM1 to stimulate TLR4/NF‐κB signaling and prohibit autophagy. Knockdown of FOXJ2, SLAMF8, or TREM1 blocks TLR4/NF‐κB and provokes autophagy, subsequently inhibiting the release of inflammatory and thrombotic indicators. A mouse model of vascular APS is established via β2GPI intraperitoneal injection, and the results suggest that OICR‐9429 administration attenuates the inflammatory response and thrombus formation by inactivating FOXJ2/SLAMF8/TREM1 signaling. These findings highlight the overexpression of H3K4me3‐mediated FOXJ2 in APS, which consequently accelerates APS pathogenesis by triggering inflammation and thrombosis via boosting the SLAMF8/TREM1 axis. Therefore, OICR‐9429 is a promising candidate drug for APS therapy.

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Section: Discussionmentioning

confidence: 70%

H3K4me3‐Mediated FOXJ2/SLAMF8 Axis Aggravates Thrombosis and Inflammation in β2GPI/Anti‐β2GPI‐Treated Monocytes

Tan,

Qiao,

Yang

et al. 2024

Advanced Science

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“…miRNAs have a significant effect on the early diagnosis and prognostic evaluation of BC and on reversing the drug resistance of cancers [ 14 ]. All kinds of miRNAs have abnormal expression in BC [ 15 , 16 ], and these maladjusted miRNAs play an antitumour or carcinogenic role in the disease and are involved in its pathological process [ 17 , 18 ]. There is abnormal expression of miR-92b-3p in colorectal cancer [ 19 , 20 ] and oesophageal squamous cell carcinoma [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Expression levels and clinical values of miR-92b-3p in breast cancer

Miao

Wang

et al. 2021

World J Surg Onc

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Background miR-92b is a carcinogenic miRNA that has great potential as a biomarker for disease prognosis, diagnosis, and treatment in the clinic. It is of great significance to analyse the relationship between miR-92b and the clinicopathological characteristics of cancer patients. This paper aimed to investigate the expression levels and clinical values of miR-92b-3p in breast cancer (BC). Methods Altogether, 112 female BC patients who were treated in our hospital were included as a study group, and 108 healthy women who came to our hospital for physical examinations were included as a control group. miR-92b-3p expression in the serum of subjects in both groups was detected by fluorescence quantitative PCR (RT-PCR) to analyse the correlation of this miRNA with the patients’ pathological features and prognoses. The diagnostic value of miR-92b-3p expression for BC was analysed by plotting a receiver operating characteristic (ROC) curve. Results miR-92b-3p expression was remarkably higher in the study group (P < 0.05), and its area under the curve (AUC) for detecting BC was 0.88. The expression was correlated with the tumour size, degree of differentiation, TNM staging, and lymphatic metastasis (P < 0.05). miR-92b-3p was significantly positively correlated with the TNM staging (r = 0.40, P < 0.05), was significantly negatively correlated with the degree of differentiation of the breast cancer cells (r = − 0.35, P < 0.05), and was significantly positively correlated with the expression of carbohydrate antigen 125 (CA125) (r = 0.39, P < 0.05). The overall survival rate (OSR) of the 99 patients who had follow-up was 73.74%. The survival status was remarkably better in the low expression group (P < 0.05). miR-92b-3p expression was remarkably higher in the death group (P < 0.05). The AUC of miR-92b-3p alone in the death and survival groups was 0.76. Conclusion miR-92b-3p expression obviously rises in the serum of BC patients and is closely related to the clinical staging, degree of differentiation, and CA125 in BC, so the detection of this miRNA is of great significance to the diagnosis and prognostic evaluation of BC. This miRNA can be used as a potential biomarker for the diagnosis and prognosis of the disease.

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“…miR-454 has been detected either as oncogenic or tumor-suppressive, strictly depending on the type of cancer. However, in the context of breast cancer, miR-454-5p was reported to be up-regulated and strongly associated with poor prognosis, as well as being capable of inducing EMT via targeting the FoxJ2/E-cadherin axis in MDA-MB-231 cells [ 52 ]. Ren et al reported that miR-454-3p was amplified and over-expressed in metastatic breast cancer and capable of enhancing BCC stemness and promoting metastasis, both in vivo and in vitro.…”

Section: Mirnas Exerting Oncogenic Functions In Bcscs and Stem-like Bccsmentioning

confidence: 99%

The Intricate Interplay between Cancer Stem Cells and Oncogenic miRNAs in Breast Cancer Progression and Metastasis

Tsintarakis,

Papalouka,

Kontarini

et al. 2023

Life

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Complex signaling interactions between cancer cells and their microenvironments drive the clonal selection of cancer cells. Opposing forces of antitumor and tumorigenic potential regulate the survival of the fittest clones, while key genetic and epigenetic alterations in healthy cells force them to transform, overcome cell senescence, and proliferate in an uncontrolled manner. Both clinical samples and cancer cell lines provide researchers with an insight into the complex structure and hierarchy of cancer. Intratumor heterogeneity allows for multiple cancer cell subpopulations to simultaneously coexist within tumors. One category of these cancer cell subpopulations is cancer stem cells (CSCs), which possess stem-like characteristics and are not easily detectable. In the case of breast cancer, which is the most prevalent cancer type among females, such subpopulations of cells have been isolated and characterized via specific stem cell markers. These stem-like cells, known as breast cancer stem cells (BCSCs), have been linked to major events during tumorigenesis including invasion, metastasis and patient relapse following conventional therapies. Complex signaling circuitries seem to regulate the stemness and phenotypic plasticity of BCSCs along with their differentiation, evasion of immunosurveillance, invasiveness and metastatic potential. Within these complex circuitries, new key players begin to arise, with one of them being a category of small non-coding RNAs, known as miRNAs. Here, we review the importance of oncogenic miRNAs in the regulation of CSCs during breast cancer formation, promotion and metastasis, in order to highlight their anticipated usage as diagnostic and prognostic tools in the context of patient stratification and precision medicine.

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MicroRNA‑454‑5p promotes breast cancer progression by inducing epithelial‑mesenchymal transition via targeting the FoxJ2/E‑cadherin axis

Cited by 7 publications

References 47 publications

H3K4me3‐Mediated FOXJ2/SLAMF8 Axis Aggravates Thrombosis and Inflammation in β2GPI/Anti‐β2GPI‐Treated Monocytes

H3K4me3‐Mediated FOXJ2/SLAMF8 Axis Aggravates Thrombosis and Inflammation in β2GPI/Anti‐β2GPI‐Treated Monocytes

Expression levels and clinical values of miR-92b-3p in breast cancer

The Intricate Interplay between Cancer Stem Cells and Oncogenic miRNAs in Breast Cancer Progression and Metastasis

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