MicroRNAs regulate the epithelial–mesenchymal transition and influence breast cancer invasion and metastasis

Zhao, Min; Lin, Ang; Huang, Jin; Wang, Jin

doi:10.1177/1010428317691682

Cited by 48 publications

(30 citation statements)

References 85 publications

(123 reference statements)

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“…Recent studies have found that ZEB1 is rarely expressed in epithelial tissues and highly differentiated tumor tissues, but it is highly expressed in poorly differentiated tumors, especially in the invasive part. 23,24 In our study, we found that up-regulated GRHL2 directly inhibited the expression of ZEB1, indirectly inhibited the expression of E-cadherin and up-regulated the expressions of Vimentin, Snail and Slug, and vice versa. This indicated that GRHL2 was crucial in regulation of EMT.…”

Section: Discussionsupporting

confidence: 49%

<p>GRHL2 Acts as an Anti-Oncogene in Bladder Cancer by Regulating ZEB1 in Epithelial-Mesenchymal Transition (EMT) Process</p>

Shen¹,

Lv²,

Zhang³

2020

OTT

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GRHL2 played important roles in different cancers. In this study, we aimed to investigate the roles of GRHL2 in bladder cancer. Methods: The immunohistochemistry assay was performed to detect the expression of GRHL2 in bladder cancer tissues and adjacent noncancerous tissues and the expression levels of GRHL2 and zinc finger E-box binding homeobox (ZEB1) mRNA in tissues were determined by qRT-PCR. In addition, qRT-PCR and Western blotting were applied to detect the expression levels of GRHL2 and ZEB1 in bladder cancer cell lines (RT4, BIU-87, 5637, T24) and immortalized human bladder epithelial cell line (SV-HUC-1). The cell models with up-regulated and down-regulated expression of GRHL2 were constructed using bladder cancer cell lines T24 and 5637 to investigate the underlying roles of GRHL2 on the proliferation, migration, invasion and EMT process of bladder cancer cells. After that, cell proliferation was evaluated by CCK8 assay, cell cycle assay and colony formation assay. Transwell assay and wound healing assay were performed to determine the invasion and migration ability of the bladder cancer cells. The expressions of epithelial-mesenchymal transition (EMT) related proteins (E-cadherin, Vimentin, Slug and Snail) were assessed by Western blot analysis. Moreover, ZEB1 and GRHL2 were co-transfected into T24 and 5637 cells and their effects on EMT process and invasive capacity of cells were examined. Results: The expression of GRHL2 was down-regulated in bladder cancer tissues and human bladder cancer cell lines compared with the normal bladder tissues and immortalized human bladder epithelial cell line. Besides, down-regulation of GRHL2 improved the proliferation ability of bladder cancer cells and promoted the EMT process through upregulation of ZEB1. The overexpression of ZEB1 partially reversed the inhibitory effect of GRHL2 on EMT. Conclusion: GRHL2 acts as an anti-oncogene to regulate bladder cancer cell proliferation and inhibit EMT by targeting ZEB1. This study may provide a theoretical basis for further research.

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Section: Discussionsupporting

confidence: 49%

<p>GRHL2 Acts as an Anti-Oncogene in Bladder Cancer by Regulating ZEB1 in Epithelial-Mesenchymal Transition (EMT) Process</p>

Shen¹,

Lv²,

Zhang³

2020

OTT

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“…miRNAs are considered as a group of small non-coding RNA molecules that exhibit different roles in some biological behaviors, for instance, cell apoptosis, differentiation, and tumorigenesis (19). Recently some studies have reported the role of miRNAs in modulating invasion and metastasis of cervical cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA BCYRN1 promotes the proliferation and metastasis of cervical cancer via targeting microRNA-138 inï¿½vitro and inï¿½vivo

et al. 2018

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Abstract. Cervical cancer is one of the most malignant types of tumor and the fourth leading cause of cancer-associated mortality in females worldwide. High expression of brain cytoplasmic RNA 1 (BCYRN1) has been detected in various tumors. The present study aimed to investigate the effect of BCYRN1 in the viability and motility of cervical cancer, and the relevant mechanism. The results demonstrated that BCYRN1 was upregulated in cervical cancer tissues compared with normal tissues. Elevated levels of BCYRN1 were also detected in three human cervical cancer cell lines (SiHa, HeLa and CaSki) compared with non-cancerous ectocervical epithelial cell line (Ect1/E6E7). The expression of BCYRN1 was suppressed following transfection with small interfering RNA (siRNA) in HeLa cells. The silence of BCYRN1 significantly reduced cell viability and motility. Furthermore, microRNA (miR)-138 was predicted as a direct target of BCYRN1 and the expression of miR-138 was elevated in HeLa cells transfected with BCYRN1 siRNA. Subsequently, elevated levels of miR-138 were suppressed by transfection with miR-138 inhibitor in HeLa cells pretreated with BCYRN1 siRNA. The targeting association between BCYRN1 and miR-138 was supported by luciferase reporter assays. Additionally, BCYRN1 siRNA partially counteracted the effect of miR-138 inhibitor on promoting cell viability and mobility in HeLa cells. Finally, the in vivo experiment verified that BCYRN1 siRNA was able to prevent tumor growth, and reduced the expression of migration marker proteins metalloproteinase 2 and vascular endothelial cell growth factor, with enhanced expression levels of miR-138. These results suggest that lncRNA BCYRN1 promotes the proliferation and invasion of cervical cancer via targeting miR-138.

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“…Many studies have shown that EMT is important for the metastasis of breast cancer [13,14]. EMT-related microRNAs can regulate EMT, invasion, and metastasis in breast cancer [15]. Twist, a key transcription factor for EMT, also promotes tumor metastasis in basal-like breast cancer [16].…”

Section: Introductionmentioning

confidence: 99%

DHA inhibits Gremlin-1-induced epithelial-to-mesenchymal transition via ERK suppression in human breast cancer cells

et al. 2020

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Docosahexaenoic acid (DHA) is an omega-3 fatty acid abundant in fish oils. It is known to have an inhibitory effect on various diseases such as inflammation, diabetes, and cancer. Epithelial-to-mesenchymal transition (EMT) is a process that epithelial cells gain migratory property to become mesenchymal cells involved in wound healing, organ fibrosis, and cancer progression. Gremlin-1 (GREM1) is a bone morphogenetic protein antagonist known to play a role in EMT. However, the role of GREM1 in the induction of EMT in human breast cancer cells and the effect of DHA on GREM1-induced EMT remain unclear. Establishment of GREM1 knockdown cell lines was performed using lentiviral shRNAs. Expression of EMT markers was determined by qRT-PCR and Western blotting. Effect of GREM1 and/or DHA on cell migration was investigated using wound healing assay. The level of GREM1 expression in human breast cancer tissues was determined by Oncomine database mining. GREM1 induced the expression of genes including N-cadherin, vimentin, and Slug. GREM1 promoted the migration of human breast cancer cells. GREM1 enhanced the expression of phosphorylated extracellular signal-regulated kinase (p-ERK) and the ERK activation was involved in EMT. Interestingly, DHA reduced the expression of GREM1. DHA also inhibited the expression of mesenchymal cell-associated genes and cell migration induced by GREM1. Furthermore, DHA suppressed the expression of p-ERK induced by GREM1. These results indicate that GREM1-ERK axis plays a role in EMT in human breast cancer cells and DHA is a putative compound that can inhibit EMT by inhibiting GREM1 signal transduction.

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MicroRNAs regulate the epithelial–mesenchymal transition and influence breast cancer invasion and metastasis

Cited by 48 publications

References 85 publications

<p>GRHL2 Acts as an Anti-Oncogene in Bladder Cancer by Regulating ZEB1 in Epithelial-Mesenchymal Transition (EMT) Process</p>

<p>GRHL2 Acts as an Anti-Oncogene in Bladder Cancer by Regulating ZEB1 in Epithelial-Mesenchymal Transition (EMT) Process</p>

Long non-coding RNA BCYRN1 promotes the proliferation and metastasis of cervical cancer via targeting microRNA-138 inï¿½vitro and inï¿½vivo

DHA inhibits Gremlin-1-induced epithelial-to-mesenchymal transition via ERK suppression in human breast cancer cells

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