miR-381-3p suppresses breast cancer progression by inhibition of epithelial–mesenchymal transition

Abstract Background Accumulating evidence indicates that miRNAs are involved in multiple cellular functions and participate in various cancer development and progression, including breast cancer. Methods We aimed to investigate the role of miR-381-3p in breast cancer. The expression level of miR-381-3p and EMT transcription factors was examined by quantitative real-time PCR (qRT-PCR). The effects of miR-381-3p on breast cancer proliferation and invasion were determined by Cell Counting Kit-8 (CCK-8), colony formation, and transwell assays. The regulation of miR-381-3p on its targets was determined by dual-luciferase analysis, qRT-PCR, and western blot. Results We found that the expression of miR-381-3p was significantly decreased in breast cancer tissues and cell lines. Overexpression of miR-381-3p inhibited breast cancer proliferation and invasion, whereas knockdown of miR-381-3p promoted cell proliferation and invasion in MDA-MB-231 and SKBR3 cells. Mechanistically, overexpression of miR-381-3p inhibited breast cancer epithelial–mesenchymal transition (EMT). Both Sox4 and Twist1 were confirmed as targets of miR-381-3p. Moreover, transforming growth factor-β (TGF-β) could reverse the effects of miR-381-3p on breast cancer progression. Conclusions Our observation suggests that miR-381-3p inhibits breast cancer progression and EMT by regulating the TGF-β signaling via targeting Sox4 and Twist1.

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Transforming growth factor-β-induced epithelial–mesenchymal transition facilitates epidermal growth factor-dependent breast cancer progression

Oncogene ◽

10.1038/onc.2010.377 ◽

2010 ◽

Vol 29 (49) ◽

pp. 6485-6498 ◽

Cited By ~ 139

Author(s):

M K Wendt ◽

J A Smith ◽

W P Schiemann

Keyword(s):

Breast Cancer ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Cancer Progression ◽

Transforming Growth Factor ◽

Epithelial Mesenchymal Transition ◽

Transforming Growth Factor Β ◽

Breast Cancer Progression ◽

Mesenchymal Transition ◽

Epidermal Growth

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PPA1 Promotes Breast Cancer Proliferation and Metastasis Through PI3K/AKT/GSK3β Signaling Pathway

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.730558 ◽

2021 ◽

Vol 9 ◽

Author(s):

Chunlei Guo ◽

Shuang Li ◽

Ang Liang ◽

Mengchao Cui ◽

Yunwei Lou ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Epithelial Mesenchymal Transition ◽

Glycogen Synthase ◽

Breast Cancer Progression ◽

Inorganic Pyrophosphatase ◽

Cancer Proliferation ◽

Mesenchymal Transition ◽

Phosphorylated Akt ◽

Proliferation And Metastasis

Breast cancer is the most common malignancy among women. Inorganic pyrophosphatase 1 (PPA1) is a multifunctional protein involved in the development of several tumors. However, the role of PPA1 in breast cancer progression remains unclear. In this study, we found that PPA1 was highly expressed in breast cancer compared to its levels in normal breast tissue and that it was correlated with breast cancer clinicopathological characteristics, as well as poor survival in breast cancer patients. Silencing PPA1 restrained breast cancer proliferation and metastasis by regulating Slug-mediated epithelial-mesenchymal transition (EMT). Opposite results were observed following PPA1 overexpression. In addition, investigation of the underlying mechanism demonstrated that PPA1 ablation led to decrease phosphatidylinositol 3 kinase (PI3K) phosphorylation levels and attenuate phosphorylated AKT and glycogen synthase kinase-3 β (GSK3β), while ectopic PPA1 expression had the opposite effects. Moreover, PI3K inhibitors suppress the signaling pathways mediating the effects of PPA1 on breast cancer, resulting in tumor growth and metastasis suppression in vitro and in vivo. In summary, our results verify that PPA1 can act as an activator of PI3K/AKT/GSK3β/Slug-mediated breast cancer progression and that it is a potential therapeutic target for the inhibition of tumor progression.

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miR-125 inhibits colorectal cancer proliferation and invasion by targeting TAZ

Bioscience Reports ◽

10.1042/bsr20190193 ◽

2019 ◽

Vol 39 (12) ◽

Cited By ~ 4

Author(s):

Meiyuan Yang ◽

Xiaoli Tang ◽

Zheng Wang ◽

Xiaoqing Wu ◽

Dong Tang ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Underlying Mechanism ◽

Cell Counting ◽

Binding Motif ◽

Cancer Proliferation ◽

Qrt Pcr ◽

Sirna Knockdown ◽

Proliferation And Invasion ◽

Hct116 Cells

Abstract Colorectal cancer (CRC) is the third most common malignant tumor worldwide and is a serious threat to human health. MicroRNAs (miRNAs) play a key role in oncogenesis and cancer progression. MiRNA-125 (miR-125) is an important miRNA that is dysregulated in several kinds of cancers. Thus, we investigated the expression and effects of miR-125 and Transcriptional co-activator with PDZ-binding motif (TAZ) for a better understanding of the underlying mechanism of tumor progression in CRC, which may provide an emerging biomarker for diagnosis and treatment of CRC. We measured the expression levels of miR-125 in CRC tissues, adjacent tissues, and cell lines (e.g. HCT116, SW480, FHC) by quantitative real-time polymerase chain reaction (qRT-PCR). The effect of miR-125 on proliferation and invasion in CRC cells was detected by Cell Counting Kit-8 (CCK-8), clone formation assay, and transwell assay. Western blotting and qRT-PCR were used to investigate the expression of TAZ after knocking down miR-125 in HCT116 cells or overexpressing miR-125 in SW480 cells. MiR-125 was significantly down-regulated in CRC compared with pericarcinomatous tissue from 18 patients. An miR-125 inhibitor promoted CRC cell proliferation and invasion, while miR-125 mimic had the opposite effect. Moreover, we found that TAZ was an miR-125 target and the siRNA knockdown of TAZ could reverse the effect of the miR-125 inhibitor on proliferation and invasion in HCT116 cells. The present study shows that miR-125 suppresses CRC proliferation and invasion by targeting TAZ.

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LINC00665 promotes breast cancer progression through regulation of the miR-379-5p/LIN28B axis

Cell Death and Disease ◽

10.1038/s41419-019-2213-x ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 7

Author(s):

Wei Ji ◽

Yu-Ling Diao ◽

Yi-Ran Qiu ◽

Jie Ge ◽

Xu-Chen Cao ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Epithelial Mesenchymal Transition ◽

Normal Breast ◽

Breast Cancer Progression ◽

Migration And Invasion ◽

Breast Tumorigenesis ◽

Mesenchymal Transition ◽

Tumorigenesis And Progression ◽

Mirna Sponges

AbstractBreast cancer is the most common malignant tumor among women worldwide. Although increasing evidence indicates that long noncoding RNAs (lncRNAs) play critical roles during breast tumorigenesis and progression, the involvement of most lncRNAs in breast cancer remains largely unknown. In the current study, we demonstrated that LINC00665 promotes breast cancer cell proliferation, migration, and invasion. Accumulating evidence indicates that many lncRNAs can function as endogenous miRNA sponges by competitively binding common miRNAs. In this study, we demonstrated that LINC00665 functions as a sponge for miR-379-5p, reducing the ability of miR-379-5p to repress LIN28B. LINC00665 promoted breast cancer progression and induced an epithelial–mesenchymal transition-like phenotype via the upregulation of LIN28B expression. Clinically, LINC00665 expression was increased but miR-379-5p expression was decreased in breast cancer tissues compared with that in normal breast tissues in the TCGA database. Furthermore, the expression of LINC00665 was negatively related with miR-379-5p expression. Collectively, our results reveal the LINC00665–miR-379-5p–LIN28B axis and shed light on breast cancer therapy.

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