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Title: miR-411-5p inhibits proliferation and metastasis of breast cancer cell via targeting GRB2

Abstract

miR-411-5p (previously called miR-411) is severely involved in human diseases, however, the relationship between miR-411-5p and breast cancer has not been investigated thoroughly. Here, we found that the expression of miR-411-5p was downregulated in breast cancer tissues compared with their matched adjacent non-neoplastic tissues. In addition, the expression of miR-411-5p was also lower in breast cancer cell lines in contrast with MCF-10A. Moreover, we investigated the target and mechanism of miR-411-5p in breast cancer using mimic and inhibitor, and demonstrated the involvement of GRB2 and Ras activation. Ectopic expression of miR-411-5p suppressed the breast cancer cell proliferation, migration and invasion while low expression of miR-411-5p exhibited the opposite effect. Furthermore, GRB2 was demonstrated to be significantly overexpressed in breast cancer tissues compared with normal tissues, and low expression of GRB2 had a longer overall survival compared with high expression of GRB2 in breast cancer. In general, our study shed light on the miR-411-5p related mechanism in the progression of breast cancer and, miR-411-5p/GRB2/Ras axis is potential to be molecular target for breast cancer therapy. - Highlights: • miR-411-5p is downregulated in breast cancer tissues and cell lines. • miR-411-5p inhibits breast cancer cells growth, migration and invasion in vitro. • GRB2more » is a direct target of miR-411-5p in breast cancer. • GRB2 is overexpressed in breast cancer and associates with disease outcome. • miR-411-5p suppresses breast cancer progression though GRB2-SOS-Ras pathway.« less

Authors:
 [1];  [2];  [1];  [2]; ;  [1];  [1];  [2];  [3]; ; ;  [1];  [2];  [1];  [2];  [1];  [2]
  1. Department of Gastrointestinal Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003 (China)
  2. (China)
  3. State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102 (China)
Publication Date:
OSTI Identifier:
22606141
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 476; Journal Issue: 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; CELL PROLIFERATION; IN VITRO; MAMMARY GLANDS; METASTASES; NEOPLASMS

Citation Formats

Zhang, Yunda, State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, Xu, Guoxing, Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005, Liu, Gang, Ye, Yongzhi, Zhang, Chuankai, State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, Fan, Chuannan, Wang, Haibin, Cai, Huali, Xiao, Rui, Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005, Huang, Zhengjie, E-mail: huangzhengjie@xmu.edu.cn, Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005, Luo, Qi, E-mail: luoqixmzsh@126.com, and Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005. miR-411-5p inhibits proliferation and metastasis of breast cancer cell via targeting GRB2. United States: N. p., 2016. Web. doi:10.1016/J.BBRC.2016.06.006.
Zhang, Yunda, State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, Xu, Guoxing, Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005, Liu, Gang, Ye, Yongzhi, Zhang, Chuankai, State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, Fan, Chuannan, Wang, Haibin, Cai, Huali, Xiao, Rui, Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005, Huang, Zhengjie, E-mail: huangzhengjie@xmu.edu.cn, Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005, Luo, Qi, E-mail: luoqixmzsh@126.com, & Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005. miR-411-5p inhibits proliferation and metastasis of breast cancer cell via targeting GRB2. United States. doi:10.1016/J.BBRC.2016.06.006.
Zhang, Yunda, State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, Xu, Guoxing, Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005, Liu, Gang, Ye, Yongzhi, Zhang, Chuankai, State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, Fan, Chuannan, Wang, Haibin, Cai, Huali, Xiao, Rui, Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005, Huang, Zhengjie, E-mail: huangzhengjie@xmu.edu.cn, Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005, Luo, Qi, E-mail: luoqixmzsh@126.com, and Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005. 2016. "miR-411-5p inhibits proliferation and metastasis of breast cancer cell via targeting GRB2". United States. doi:10.1016/J.BBRC.2016.06.006.
@article{osti_22606141,
title = {miR-411-5p inhibits proliferation and metastasis of breast cancer cell via targeting GRB2},
author = {Zhang, Yunda and State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102 and Xu, Guoxing and Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005 and Liu, Gang and Ye, Yongzhi and Zhang, Chuankai and State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102 and Fan, Chuannan and Wang, Haibin and Cai, Huali and Xiao, Rui and Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005 and Huang, Zhengjie, E-mail: huangzhengjie@xmu.edu.cn and Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005 and Luo, Qi, E-mail: luoqixmzsh@126.com and Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005},
abstractNote = {miR-411-5p (previously called miR-411) is severely involved in human diseases, however, the relationship between miR-411-5p and breast cancer has not been investigated thoroughly. Here, we found that the expression of miR-411-5p was downregulated in breast cancer tissues compared with their matched adjacent non-neoplastic tissues. In addition, the expression of miR-411-5p was also lower in breast cancer cell lines in contrast with MCF-10A. Moreover, we investigated the target and mechanism of miR-411-5p in breast cancer using mimic and inhibitor, and demonstrated the involvement of GRB2 and Ras activation. Ectopic expression of miR-411-5p suppressed the breast cancer cell proliferation, migration and invasion while low expression of miR-411-5p exhibited the opposite effect. Furthermore, GRB2 was demonstrated to be significantly overexpressed in breast cancer tissues compared with normal tissues, and low expression of GRB2 had a longer overall survival compared with high expression of GRB2 in breast cancer. In general, our study shed light on the miR-411-5p related mechanism in the progression of breast cancer and, miR-411-5p/GRB2/Ras axis is potential to be molecular target for breast cancer therapy. - Highlights: • miR-411-5p is downregulated in breast cancer tissues and cell lines. • miR-411-5p inhibits breast cancer cells growth, migration and invasion in vitro. • GRB2 is a direct target of miR-411-5p in breast cancer. • GRB2 is overexpressed in breast cancer and associates with disease outcome. • miR-411-5p suppresses breast cancer progression though GRB2-SOS-Ras pathway.},
doi = {10.1016/J.BBRC.2016.06.006},
journal = {Biochemical and Biophysical Research Communications},
number = 4,
volume = 476,
place = {United States},
year = 2016,
month = 8
}
  • Highlights: • MiR-132 is down-regulated in breast cancer tissues and cell lines. • MiR-132 directly regulates HN1 by binding its 3′ UTR. • MiR-132 shows regulatory role in proliferation, invasion, migration and metastasis. • HN1 is involved in miR-132-mediated cell behavior. • Aberrant HN1 is associated with worse overall survival of breast cancer patients. - Abstract: Accumulating evidence indicates that miRNAs play critical roles in tumorigenesis and cancer progression. This study aims to investigate the role and the underlying mechanism of miR-132 in breast cancer. Here, we report that miR-132 is significantly down-regulated in breast cancer tissues and cancer cellmore » lines. Additional study identifies HN1 as a novel direct target of miR-132. MiR-132 down-regulates HN1 expression by binding to the 3′ UTR of HN1 transcript, thereby, suppressing multiple oncogenic traits such as cancer cell proliferation, invasion, migration and metastasis in vivo and in vitro. Overexpression of HN1 restores miR-132-suppressed malignancy. Importantly, higher HN1 expression is significantly associated with worse overall survival of breast cancer patients. Taken together, our data demonstrate a critical role of miR-132 in prohibiting cell proliferation, invasion, migration and metastasis in breast cancer through direct suppression of HN1, supporting the potential utility of miR-132 as a novel therapeutic strategy against breast cancer.« less
  • Microarray data analyses were performed to search for metastasis-associated oncogenes in prostate cancer (PCa). RNF31 mRNA expressions in tumor tissues and benign prostate tissues were evaluated. The RNF31 protein expression levels were also analyzed by western blot and immunohistochemistry. Luciferase reporter assays were used to identify miRNAs that can regulate RNF31. The effect of RNF31 on PCa progression was studied in vitro and in vivo. We found that RNF31 was significantly increased in PCa and its expression level was highly correlated with seminal vesicle invasion, clinical stage, prostate specific antigen (PSA) level, Gleason score, and BCR. Silence of RNF31 suppressed PCa cellmore » proliferation and metastasis in vitro and in vivo. miR-503 can directly regulate RNF31. Enforced expression of miR-503 inhibited the expression of RNF31 significantly and the restoration of RNF31 expression reversed the inhibitory effects of miR-503 on PCa cell proliferation and metastasis. These findings collectively indicated an oncogene role of RNF31 in PCa progression which can be regulated by miR-503, suggesting that RNF31 could serve as a potential prognostic biomarker and therapeutic target for PCa. - Highlights: • RNF31 is a potential metastasis associated gene and is associated with prostate cancer progression. • Silence of RNF31 inhibits PCa cell colony formation, migration and invasion. • RNF31 as a direct target of miR-503. • miR-503 can regulate cell proliferation, invasion and migration by targeting RNF31. • RNF31 plays an important role in PCa growth and metastasis in vivo.« less
  • MicroRNAs (miRNAs) represent an abundant group of small non-coding RNAs that regulate gene expression, and have been demonstrated to play roles as tumor suppressor genes (oncogenes), and affect homeostatic processes such as development, cell proliferation, and cell death. Subsequently, epidermal growth factor-like domain 7 (EGFL7), which is confirmed to be involved in cellular responses such as cell migration and blood vessel formation, is identified as a potential miR-126 target by bioinformatics. However, there is still no evidence showing EGFL7's relationship with miR-126 and the proliferation of lung cancer cells. The aim of this work is to investigate whether miR-126, togethermore » with EGFL7, have an effect on non-small cell lung cancer (NSCLC) cells' proliferation. Therefore, we constructed overexpressed miR-126 plasmid to target EGFL7 and transfected them into NSCLC cell line A549 cells. Then, we used methods like quantitative RT-PCR, Western blot, flow cytometry assay, and immunohistochemistry staining to confirm our findings. The result was that overexpression of miR-126 in A549 cells could increase EGFL7 expression. Furthermore, the most notable finding by cell proliferation related assays is that miR-126 can inhibit A549 cells proliferation in vitro and inhibit tumor growth in vivo by targeting EGFL7. As a result, our study demonstrates that miR-126 can inhibit proliferation of non-small cell lung cancer cells through one of its targets, EGFL7.« less
  • microRNAs (miRNAs) play a vital role in tumor development and progression. In this study, we aimed to determine the expression and biological roles of miR-328 in cervical cancer and identify its direct target gene. Our data showed that miR-328 was significantly downregulated in human cervical cancer tissues and cells. Re-expression of miR-328 inhibited cervical cancer cell proliferation and colony formation in vitro and suppressed the growth of xenograft tumors in vivo. Bioinformatic analysis predicted TCF7L2 (an essential effector of canonical Wnt signaling) as a target gene of miR-328, which was confirmed by luciferase reporter assays. Enforced expression of miR-328 led to amore » decline in the expression of endogenous TCF7L2 in cervical cancer cells. In cervical cancer tissues, TCF7L2 protein levels were negatively correlated with miR-328 expression levels (r = −0.462, P = 0.017). Small interfering RNA-mediated knockdown of TCF7L2 significantly impaired the proliferation and colony formation of cervical cancer cells. Ectopic expression of a miRNA-resistant form of TCF7L2 significantly reversed the growth suppressive effects of miR-328 on cervical cancer cells, which was accompanied by induction of cyclin D1 expression. Taken together, our results provide first evidence for the growth suppressive activity of miR-328 in cervical cancer, which is largely ascribed to downregulation of TCF7L2. Restoration of miR-328 may have therapeutic potential in cervical cancer. -- Highlights: •miR-328 inhibits cervical cancer cell growth and tumorigenesis. •TCF7L2 is a direct target gene of miR-328 in cervical cancer. •Knockdown of TCF7L2 impairs the proliferation and colony formation of cervical cancer cells.« less
  • Highlights: • miR-30a represses Eya2 expression by binding to the 3′-untranslated region of Eya2. • The miR-30a/EYA2 axis regulates breast cancer cell proliferation and migration. • The miR-30a/EYA2 axis modulates G1/S cell cycle progression. • The miR-30a/EYA2 axis is dysregulated in breast cancer patients. - Abstract: Eye absent (Eya) proteins are involved in cell fate determination in a broad spectrum of cells and tissues. Aberrant expression of Eya2 has been documented in a variety of cancers and correlates with clinical outcome. However, whether microRNAs (miRNAs) can regulate Eya2 expression remains unknown. Here, we show that miR-30a represses Eya2 expression bymore » binding to the 3′-untranslated region of Eya2. Overexpression of Eya2 in miR-30a-transfected breast cancer cells effectively rescued the inhibition of cell proliferation and migration caused by miR-30a. Knockdown of Eya2 by small-interfering RNA (siRNA) in breast cancer cells mimicked the effect induced by miR-30a and abolished the ability of miR-30a to regulate breast cancer cell proliferation and migration. The miR-30a/Eya2 axis could regulate G1/S cell cycle progression, accompanied by the modulation of expression of cell cycle-related proteins, including cyclin A, cyclin D1, cyclin E, and c-Myc. Moreover, miR-30a expression was downregulated in breast cancer patients, and negatively correlated with Eya2, which was upregulated in breast cancer patients. These data suggest that the miR-30a/Eya2 axis may play an important role in breast cancer development and progression and that miR-30a activation or Eya2 inhibition may be a useful strategy for cancer treatment.« less