miR‐199a‐5p regulates β1 integrin through Ets‐1 to suppress invasion in breast cancer

Li, Wentong; Wang, Hui; Zhang, Jinbao; Zhai, Limin; Chen, Weijuan; Zhao, Chunling

doi:10.1111/cas.12952

Cited by 45 publications

(35 citation statements)

References 26 publications

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“…Consistent with these results, the levels of miR‐199 family members are downregulated in metastatic lesions in contrast with the primary tumor as seen in clinical samples of colon cancers, and miR‐199 suppresses colon cancer metastasis in vivo . It has been suggested that the miR‐199 family regulates the progression and metastasis of various cancers other than colon cancer, including liver, ovarian, prostate, and breast cancers .…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miR‐199a/b‐5p is associated with GCNT2 induction upon epithelial–mesenchymal transition in colon cancer

Chao

Huang

et al. 2017

FEBS Letters

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β-1,6-N-acetylglucosaminyltransferase 2 (GCNT2), which encodes a key glycosyltransferase for blood group I antigen synthesis, is induced upon epithelial-mesenchymal transition (EMT). Our results indicate that GCNT2 is upregulated upon EMT induced with epidermal growth factor and basic FGF in cultured human colon cancer cells. GCNT2 knockdown or overexpression decreases or increases, respectively, malignancy-related characteristics of colon cancer cells and I antigen levels. MiR-199a/b-5p is markedly downregulated upon EMT in colon cancer cells. Here, we find that miR-199a/b-5p consistently regulates GCNT2 expression in reporter assays and that it binds directly to the GCNT2 3' untranslated region intracellularly in RNA-induced silencing complex-trap assays. Overexpression of miR-199a/b-5p decreases GCNT2 expression and suppresses I antigen production. Based on these findings, we propose that miR-199a/b-5p regulates GCNT2 and I antigen expression in colon cancer cells undergoing EMT.

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Section: Discussionmentioning

confidence: 99%

Downregulation of miR‐199a/b‐5p is associated with GCNT2 induction upon epithelial–mesenchymal transition in colon cancer

Chao

Huang

et al. 2017

FEBS Letters

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“…44 Villari et al group was able to identify interaction between fascin and FAK that in turn controls focal adhesion stability and motility. 48 Elevated expression of fascin and ITGB1 were independently reported in various cancers including breast and were found to associate with enhanced self-renewability, which present serious challenge to effective treatment of cancer. It is possible to speculate that fascin influences β1 integrin expression and its downstream-related function via targeting selected miRNAs, which have gained much attention in recent years due to their functions in RNA silencing and post-transcriptional regulation of gene expression.…”

Section: Discussionmentioning

confidence: 99%

β1 Integrin is essential for fascin‐mediated breast cancer stem cell function and disease progression

Barnawi

Al-Khaldi

Çolak

et al. 2019

Intl Journal of Cancer

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Breast cancer remains the second cause of tumor‐related mortality in women worldwide mainly due to chemoresistance and metastasis. The chemoresistance and metastasis are attributed to a rare subpopulation with enriched stem‐like characteristics, thus called Cancer Stem Cells (CSCs). We have previously reported aberrant expression of the actin‐bundling protein (fascin) in breast cancer cells, which enhances their chemoresistance, metastasis and enriches CSC population. The intracellular mechanisms that link fascin with its downstream effectors are not fully elucidated. Here, loss and gain of function approaches in two different breast cancer models were used to understand how fascin promotes disease progression. Importantly, findings were aligned with expression data from actual breast cancer patients. Expression profiling of a large breast cancer dataset (TCGA, 530 patients) showed statistically significant correlation between fascin expression and a key adherence molecule, β1 integrin (ITGB1). In vitro manipulation of fascin expression in breast cancer cells exhibited its direct effect on ITGB1 expression. Fascin‐mediated regulation of ITGB1 was critical for several breast cancer cell functions including adhesion to different extracellular matrix, self‐renewability and chemoresistance. Importantly, there was a significant relationship between fascin and ITGB1 co‐expression and short disease‐free as well as overall survival in chemo‐treated breast cancer patients. This novel role of fascin effect on ITGB1 expression and its outcome on cell self‐renewability and chemoresistance strongly encourages for dual targeting of fascin‐ITGB1 axis as a therapeutic approach to halt breast cancer progression and eradicate it from the root.

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“…It is well known that miRNAs function via regulating their target protein by binding to the 3’ untranslated regions (UTRs) of target messenger RNAs (mRNAs), resulting in mRNA degradation or the blockade of mRNA translation . Previously, miR‐199a‐5p was reported to functions as a tumor suppressor by targeting connective tissue growth factor (CTGF), integrin β1, hypoxia‐inducible factor 1 alpha (HIF‐1α), E‐cadherin, hexokinase 2, frizzled class receptor 6 (FZD6), E2F transcription factor 3 (E2F3), Wnt family member 2 (WNT2) and cyclin‐dependent kinase inhibitor 1C (P57, CDKN1C) …”

Section: Discussionmentioning

confidence: 99%

“…In present study, we showed that miR-199a-5p, frequently down- 19,20 Previously, miR-199a-5p was reported to functions as a tumor suppressor by targeting connective tissue growth factor (CTGF), integrin β1, hypoxia-inducible factor 1 alpha (HIF-1α), E-cadherin, hexokinase 2, frizzled class receptor 6 (FZD6), E2F transcription factor 3 (E2F3), Wnt family member 2 (WNT2) and cyclin-dependent kinase inhibitor 1C (P57, CDKN1C). [21][22][23][24][25][26][27][28][29] Clathrin is considered the prototype vesicle coat protein whose self-assembly mediates sorting of membrane cargo and recruitment of lipid modifiers. 30 In the past decades, most of studies were focused on clathrin mediated endocytosis.…”

Section: Discussionmentioning

confidence: 99%

MiR‐199a‐5p suppresses tumorigenesis by targeting clathrin heavy chain in hepatocellular carcinoma

Huang

Song

et al. 2017

Cell Biochemistry & Function

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The deregulation of microRNA (miRNA) is frequently associated with a variety of cancers, including hepatocellular carcinoma (HCC). In this study, we investigated the expression and possible role of miR-199a-5p in HCC. The expression of miR-199a-5p was measured by quantitative RT-PCR in HCC. The effect of miR-199a-5p was evaluated by cell viability and colony formation assays in HCC cell lines and tumor cell growth assay in xenograft nude mice. Quantitative real time PCR results showed that miR-199a-5p was down-regulated in 77.9 % (67/86) of HCC tissues compared with adjacent nontumor tissues. MiR-199a-5p mimic reduced cell viability and colony formation by induction of cell arrest in HCC cell lines and inhibited tumor cell growth in xenograft nude mice, but miR-199a-5p inhibitor increased cell viability and colony formation in HCC cell lines and tumor cell growth in xenograft nude mice. Furthermore, CLTC was defined as a potential direct target of miR-199a-5p by MiRanda and TargetScan predictions. The dual-luciferase reporter gene assay results showed that CLTC was a direct target of miR-199a-5p. The use of miR-199a-5p mimic or inhibitor could decrease or increase CLTC protein levels in HCC cell lines. We conclude that the frequently down-regulated miR-199a-5p can regulate CLTC and might function as a tumor suppressor in HCC. Therefore, miR-199a-5p may serve as a useful therapeutic agent for miRNA-based HCC therapy.

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miR‐199a‐5p regulates β1 integrin through Ets‐1 to suppress invasion in breast cancer

Cited by 45 publications

References 26 publications

Downregulation of miR‐199a/b‐5p is associated with GCNT2 induction upon epithelial–mesenchymal transition in colon cancer

Downregulation of miR‐199a/b‐5p is associated with GCNT2 induction upon epithelial–mesenchymal transition in colon cancer

β1 Integrin is essential for fascin‐mediated breast cancer stem cell function and disease progression

MiR‐199a‐5p suppresses tumorigenesis by targeting clathrin heavy chain in hepatocellular carcinoma

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