scholarly journals MiR-142-5p Acts as a Significant Regulator Through Promoting Proliferation, Invasion, and Migration in Breast Cancer Modulated by Targeting SORBS1

2019 ◽  
Vol 18 ◽  
pp. 153303381989226 ◽  
Author(s):  
Weixuan Yu ◽  
Dongwei Li ◽  
Yunda Zhang ◽  
Cheukfai Li ◽  
Chuanzhao Zhang ◽  
...  

Background: Numerous researches have demonstrated that miR-142-5p plays significant roles in several cancers, although the functional characteristic of miR-142-5p in breast cancer has not been determined. This study is designed to explore the biological significance of miR-142-5p in breast cancer clinical implication and mechanism of action. Methods: The differential expression patterns of miR-142-5p and Sorbin and SH3 domain-containing protein 1 and correlations between them and clinical significances were analyzed based on data from database. The expression levels of miR-142-5p in breast cancer cells were detected using quantitative real-time polymerase chain reaction. Cell counting kit-8, transwell, and wound healing assays were used to explore the potential functions of miR-142-5p in breast cancer cells. In addition, bioinformatics prediction analysis and luciferase reporter assay were utilized to predict and identify the potential target gene of miR-142-5p. A rescue experiment was conducted by transfecting miR-142-5p inhibitors and si-Sorbin and SH3 domain-containing protein 1 into cells to explore miR-142-5p/Sorbin and SH3 domain-containing protein 1 pairs on breast cancer cells behaviors. Results: The analysis results showed that miR-142-5p was highly expressed in patients with breast cancer, while Sorbin and SH3 domain-containing protein 1 presented a trend of low expression. The clinical significances analysis suggested that the overexpression of miR-142-5p is closely correlated with metastasis, while low expression of Sorbin and SH3 domain-containing protein 1 is correlated with clinicopathological characteristics and poor overall survival in patients with breast cancer. In vitro exploration, the expression of miR-142-5p was upregulated in breast cancer cells and inhibition of miR-142-5p expression significantly reduced the proliferation, invasion, and migration of breast cancer cells. Through rescue experiments, breast cancer cells proliferation, invasion, and migration reduction induced by silencing of miR-142-5p were reversed via knockdown Sorbin and SH3 domain-containing protein 1. Conclusion: Our findings insinuate that miR-142-5p functions as a positive regulator of promoting breast cancer cells biological behaviors and clinical metastasis, possibly regulated by targeting Sorbin and SH3 domain-containing protein 1, thus providing valuable information in the development of preventive or even therapeutic strategies for utilizing miR-142-5p as a promising target.

2019 ◽  
Vol 51 (10) ◽  
pp. 1008-1015 ◽  
Author(s):  
Shusheng Qiu ◽  
Wei Hu ◽  
Qiuhong Ma ◽  
Yi Zhao ◽  
Liang Li ◽  
...  

Abstract Tumor necrosis factor α-induced protein 8-like-1 (TIPE1) functions as an activator or a repressor in a tumor cell type-specific manner. However, the role of TIPE1 in breast cancer, especially regarding metastasis, is unknown. In this study, we aimed to investigate the TIPE1 expression in breast cancer tissues, the biological functions, and the underlying mechanisms of TIPE1 regarding the metastatic properties of breast cancer cells. The results of immunohistochemical staining and western blot analysis indicated that TIPE1 expression was associated with tumor size and lymph node metastasis, and the expression of TIPE1 was downregulated in the tissues of patients with lymph node metastasis. Transwell and wound healing assay results showed that TIPE1 inhibited the invasive and migratory capacities of breast cancer cells. Moreover, the epithelial-mesenchymal transition (EMT) was suppressed in TIPE1-overexpressing cells, as demonstrated by western blot analysis. In addition, western blot analysis also showed that TIPE1 reduced the expression levels of MMP2 and MMP9 and decreased the phosphorylation level of ERK. These results suggested that TIPE1 might suppress the invasion and migration of breast cancer cells and inhibit EMT primarily via the ERK signaling pathway. Our findings revealed the anti-tumor metastasis role of TIPE1 in breast cancer and TIPE1 might be a new candidate prognostic indicator and a potential molecular target for the treatment of breast cancer.


2020 ◽  
Vol 29 (2) ◽  
pp. 277-290
Author(s):  
Xuan Liu ◽  
Weirong Yao ◽  
Haiwei Xiong ◽  
Qiang Li ◽  
Yingliang Li

BACKGROUND: Breast cancer is the most common malignant tumor and usually occurs in women. Studies have shown that lncRNA nuclear enriched abundant transcript 1 (NEAT1) contributes to breast cancer progression. This study intends to further investigate the molecular mechanism of NEAT1 in breast cancer. METHODS: The expression levels of NEAT1, miR-410-3p and Cyclin D1 (CCND1) were detected by quantitative real-time PCR (qRT-PCR) in breast cancer tissues and cells. Kaplan-Meier analysis and the log-rank test were performed to determine the relationship between NEAT1 and overall survival. Cell Counting Kit-8 (CCK-8) assay analyzed cell proliferation. Transwell assay was performed to examine cell migration and invasion. The protein levels of CCND1 and epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin and Vimentin) were measured by western blot. The target relationship was predicted by bioinformatics analysis, and confirmed by luciferase reporter assay and RNA Immunoprecipitation (RIP) assay. Xenograft analysis was used to evaluate the tumor growth in vivo. RESULTS: NEAT1 and CCND1 were upregulated, while miR-410-3p was down-regulated in breast cancer tissues and cells. Higher NEAT1 expression level was associated with lower survival rate of breast cancer patients. Knockdown of miR-410-3p restored silenced NEAT1-mediated the inhibition of on proliferation, migration, invasion and EMT of breast cancer cells. In addition, NEAT1 regulated CCND1 expression by sponging miR-410-3p in breast cancer cells. NEAT1 knockdown blocked the tumor growth in vivo. CONCLUSION: NEAT1 induced breast cancer progression by regulating the miR-410-3p/CCND1 axis, indicating that NEAT1 may be a potential therapeutic target in breast cancer.


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