<scp>miR</scp>‐92a‐3p promotes breast cancer proliferation by regulating the <scp>KLF2</scp>/<scp>BIRC5</scp> axis

Yu, Zuwei; Chen, Zhaohui; Zhou, Guang-Lei; Zhou, Xue-Jie; Ma, Haiyan; Yu, Yue; Wang, Xin; Cao, Xuchen

doi:10.1111/1759-7714.14648

Cited by 10 publications

(7 citation statements)

References 35 publications

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“…We observed similar results in 33 pairs of paracancer and breast cancer tissues, but further investigation with a larger sample size is needed to confirm the relationship between KLF2 and ER, PR, and HER2 in clinical tissue samples. Therefore, our findings suggest that KLF2 may function as a tumor suppressor in breast cancer, consistent with previous reports (Hu et al, 2019;Yu et al, 2022).…”

Section: Discussionsupporting

confidence: 93%

KLF2 is a clinical diagnostic and treatment biomarker of breast cancer

Xie

Wang

et al. 2023

Front. Cell Dev. Biol.

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Background: As a highly prevalent malignancy among women worldwide, breast cancer, remains a critical public health issue necessitating the development of novel therapeutics and biomarkers. Kruppel Like Factor 2 (KLF2), a member of the Kruppel family of transcription factors, has been implicated in various types of cancer due to its diminished expression; however, the potential implications of KLF2 expression in relation to breast cancer progression, prognosis, and therapy remain unclear.Methods: The present study employed the Tumor Immune Estimation Resource (TIMER) and The Human Protein Atlas databases to investigate the expression pattern of KLF2 in pan-cancer. The relationship between KLF2 expression and clinical features or immune infiltration of The Cancer Genome Atlas (TCGA) breast cancer samples was evaluated using Breast Cancer Integrative Platform (BCIP) and TIMER. The expression levels of KLF2 in breast cancer were validated via immunohistochemical staining analysis. Gene Set Enrichment Analysis (GSEA) to study the KLF2-related gene ontology. STRING database was employed to construct a protein-protein interaction (PPI) network of KLF2 in relation to vascular endothelial growth factor A (VEGFA) and hypoxia-inducible factor 1α (HIF1α). The expression of KLF2 following diverse breast cancer therapies was analyzed in the Gene Expression Omnibus (GEO) databases. The expression of KLF2 following treatment with simvastatin was validated via immunofluorescence and western blotting.Results: Our study reveals that KLF2 displays significantly reduced expression in cancerous tissues compared to non-cancerous controls. Patients with low KLF2 expression levels exhibited poor prognosis across multiple cancer types. KLF2 expression levels were found to be reduced in advanced cancer stages and grades, while positively correlated with the expression of estrogen receptor (ER), progesterone receptor (PR), and tumor size in breast cancer. KLF2 expression is associated with diverse immune infiltration cells, and may impact the breast tumor immune microenvironment by regulating dendritic cell activation. Additionally, we observed a negative correlation between KLF2 expression levels and angiogenesis, as well as the expression of VEGFA and HIF1α. Notably, the anticancer drug simvastatin could induce KLF2 expression in both breast cancer.Conclusion: Based on our observations, KLF2 has potential as a diagnostic, prognostic, and therapeutic biomarker for breast cancer.

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Section: Discussionsupporting

confidence: 93%

KLF2 is a clinical diagnostic and treatment biomarker of breast cancer

Xie

Wang

et al. 2023

Front. Cell Dev. Biol.

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“…41 miR-92a-3p causes cell cycle arrest in S-phase in cervical cancer cells via LATS1 42 and reverses cell cycle S-phase arrest by regulating KLF2 in breast cancer. 43 In the present study, we inhibited miR-92a-3p in HQ19 to reduce the S-phase ratio and cause cell cycle block in the G2/M phase.…”

Section: Discussionmentioning

confidence: 74%

“…For example, in related literature, lncRNA GAS5 in triple‐negative breast cancer is involved in regulating cell survival under stress 41 . miR‐92a‐3p causes cell cycle arrest in S‐phase in cervical cancer cells via LATS1 42 and reverses cell cycle S‐phase arrest by regulating KLF2 in breast cancer 43 . In the present study, we inhibited miR‐92a‐3p in HQ19 to reduce the S‐phase ratio and cause cell cycle block in the G2/M phase.…”

Section: Discussionmentioning

confidence: 99%

Effect of mir‐92a‐3p on hydroquinone induced changes in human lymphoblastoid cell cycle and apoptosis

Xuan

Wang

et al. 2023

Environmental Toxicology

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Hydroquinone (HQ), one of the metabolites of benzene in humans, has significant hepatotoxic properties. Chronic exposure to HQ can lead to leukemia. In a previous study by this group, we constructed a model of malignant transformation of human lymphoblastoid cells (TK6) induced by chronic exposure to HQ with significant subcutaneous tumorigenic capacity in nude mice. miR‐92a‐3p is a tumor factor whose role in HQ‐induced malignant transformation is not yet clear. In the present study, raw signal analysis and dual‐luciferase reporter gene results suggested that miR‐92a‐3p could target and regulate TOB1, and the expression level of miR‐92a‐3p was significantly upregulated in the long‐term HQ‐induced TK6 malignant transformation model, while the anti‐proliferative factor TOB1 was significantly downregulated. To investigate the mechanism behind this, we inhibited miR‐92a‐3p in a malignant transformation model and found a decrease in cell viability, a decrease in MMP‐9 protein levels, a G2/M phase block in the cell cycle, and an upregulation of the expression of G2/M phase‐related proteins cyclinB1 and CDK1. Inhibition of miR‐92a‐3p in combination with si‐TOB1 restored cell viability, inhibited cyclin B1 and CDK1 protein levels, and attenuated the G2/M phase block. Taken together, miR‐92a‐3p reduced the cell proliferation rate of HQ19 and caused cell cycle arrest by targeting TOB1, which in turn contributed to the altered malignant phenotype of the cells. This study suggests that miR‐92a‐3p is likely to be a biomarker for long‐term HQ‐induced malignant transformation of TK6 and could be a potential therapeutic target for leukemia caused by long‐term exposure to HQ.

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“…We describe the differential expression of three winner miRNAs, two with over-expression (hsa-miR-92a-3p, hsa-miR-451a) and one dysregulated (hsa-miR-126-3p), compared to sex-and age-matched non-tumor controls. In the molecular signature found in this study, hsa-miR-92a-3p has been described as a promoter of cell proliferation in breast cancer cells by modulating Krüppel-like transcription factors (KLFs) [28]. Regarding the inclusion of this miRNA in EVs, a recent study by Uehara et al uses a mouse model to demonstrate that miRNA-92a-3p contained in EVs promotes osteolytic metastasis by directly blocking PTEN in mature osteoclasts [29].…”

Section: Exosomal Mirnas In Gastric Cancermentioning

confidence: 70%

“…The copyright holder for this preprint (which this version posted April 29, 2023. ; https://doi.org/10.1101/2023.04. 28.538562 doi: bioRxiv preprint…”

Section: Introductionmentioning

confidence: 99%

Exosomal microRNA signature from plasma-derived extracellular vesicles in gastric cancer

Rincón-Riveros¹,

Motta

Villegas

et al. 2023

Preprint

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Gastric cancer is a heterogeneous pathology that represents the fifth most frequent malignancy in the world, with more than 750,000 deaths by 2020. With significant repercussions in public health, this pathology lacks biomarkers for early diagnosis, with endoscopy biopsy being the golden test for its detection. In the exploration of new strategies to control gastric cancer in recent years, liquid biopsy appears as a potential source of biomarkers using non-invasive procedures. Here we present the characterization of miRNAs contained in plasma-derived exosomes from patients with gastric cancer. Extracellular vesicles (EVs) were isolated using size-exclusion chromatography (SEC) and their characterization was performed by electron microscopy, protein expression, and nanoparticle analysis techniques. Total RNA from isolated exosomes was obtained for small RNA-seq analysis. Transcriptomic miRNA data were used to identify differentially expressed miRNAs between patients with benign and malignant gastric diseases, which resulted in a molecular signature of nine miRNAs, that were used in a regression model to classify individuals as either having benign or malignant disease. Further, we compared benign-malignant patients at different stages of gastric cancer, and we detected 15 differentially expressed miRNAs. Among these 15 miRNAs, miR-92a-3p, miR451a, and miR126-3p were identified as winners due to their clinical and regulatory relevance. Our results offer relevant information of a Colombian case study allowing us to propose three transcriptomic gastric cancer biomarkers in liquid biopsy.

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miR‐92a‐3p promotes breast cancer proliferation by regulating the KLF2/BIRC5 axis

Cited by 10 publications

References 35 publications

KLF2 is a clinical diagnostic and treatment biomarker of breast cancer

KLF2 is a clinical diagnostic and treatment biomarker of breast cancer

Effect of mir‐92a‐3p on hydroquinone induced changes in human lymphoblastoid cell cycle and apoptosis

Exosomal microRNA signature from plasma-derived extracellular vesicles in gastric cancer

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