MiR-106b and miR-93 regulate cell progression by suppression of PTEN via PI3K/Akt pathway in breast cancer

被引:172
作者
Li, Nana [1 ]
Miao, Yuan [1 ]
Shan, Yujia [1 ]
Liu, Bing [1 ]
Li, Yang [1 ]
Zhao, Lifen [1 ]
Jia, Li [1 ]
机构
[1] Dalian Med Univ, Coll Lab Med, 9 Lvshunnan Rd Xiduan, Dalian 116044, Liaoning Provin, Peoples R China
基金
中国国家自然科学基金;
关键词
HUMAN PROSTATE-CANCER; COLORECTAL-CANCER; TUMOR-GROWTH; HEPATOCELLULAR-CARCINOMA; SIGNALING PATHWAY; DOWN-REGULATION; EXPRESSION; INVASION; MICRORNA-93; ACTIVATION;
D O I
10.1038/cddis.2017.119
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Accumulating evidences have revealed that dysregulated microRNAs (miRNAs) involve in the tumorigenesis, progression and even lead to poor prognosis of various carcinomas, including breast cancer. MiRNA-106b-5p (miR-106b) and miRNA-93-5p (miR-93) levels were confirmed to be significantly upregulated in breast cancer clinical samples (n = 36) and metastatic cell line (MDA-MB-231) compared with those in the paired adjacent tissues and normal breast epithelial cell line (MCF-10A). Moreover, further research stated that the capability of migration, invasion and proliferation changed along with the altered expression of miR-106b and miR-93 in breast cancer. PTEN, the tumor-suppressor gene, was discovered to be reduced in breast cancer tissues or MDA-MB-231 cells with high levels of miR-106b and miR-93, which were inversely expressed in PTEN overexpression tissues or cells. Based on the investigation, miR-106b and miR-93 induced the migration, invasion and proliferation and simultaneously enhanced the activity of phosphatidylinositol-3 kinase (PI3K)/Akt pathway of MCF-7 cells, which could be blocked by upregulation of PTEN. Furthermore, suppression of PTEN reversed the function induced by anti-miR-106b and anti-miR-93 in MDA-MB-231 cells, indicating that PTEN was directly targeted by these miRNAs and acted as the potential therapeutic target for breast cancer therapy. In short, reductive PTEN mediated by miR-106b and miR-93 promoted cell progression through PI3K/Akt pathway in breast cancer.
引用
收藏
页码:e2796 / e2796
页数:11
相关论文
共 39 条
[1]   miR-10b expression in breast cancer stem cells supports self-renewal through negative PTEN regulation and sustained AKT activation [J].
Bahena-Ocampo, Ivan ;
Espinosa, Magali ;
Ceballos-Cancino, Gisela ;
Lizarraga, Floria ;
Campos-Arroyo, Denise ;
Schwarz, Angela ;
Maldonado, Vilma ;
Melendez-Zajgla, Jorge .
EMBO REPORTS, 2016, 17 (05) :648-658
[2]   Reduced expression of PTEN correlates with breast cancer progression [J].
Bose, S ;
Crane, A ;
Hibshoosh, H ;
Mansukhani, M ;
Sandweis, L ;
Parsons, R .
HUMAN PATHOLOGY, 2002, 33 (04) :405-409
[3]   microRNA-106b-mediated down-regulation of C1orf24 expression induces apoptosis and suppresses invasion of thyroid cancer [J].
Carvalheira, Gianna ;
Nozima, Bruno Heidi ;
Cerutti, Janete Maria .
ONCOTARGET, 2015, 6 (29) :28357-28370
[4]   miR-93/miR-106b/miR-375-CIC-CRABP1: a novel regulatory axis in prostate cancer progression [J].
Choi, Nahyun ;
Park, Jongmin ;
Lee, Jeon-Soo ;
Yoe, Jeehyun ;
Park, Guk Yeol ;
Kim, Eunjeong ;
Jeon, Hyeongrin ;
Cho, Yong Mee ;
Roh, Tae-Young ;
Lee, Yoontae .
ONCOTARGET, 2015, 6 (27) :23533-23547
[5]   Membrane-binding and activation mechanism of PTEN [J].
Das, S ;
Dixon, JE ;
Cho, WW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (13) :7491-7496
[6]   Loss of expression of the PTEN gene protein product is associated with poor outcome in breast cancer [J].
Depowski, PL ;
Rosenthal, SI ;
Ross, JS .
MODERN PATHOLOGY, 2001, 14 (07) :672-676
[7]   Breast cancer statistics, 2011 [J].
DeSantis, Carol ;
Siegel, Rebecca ;
Bandi, Priti ;
Jemal, Ahmedin .
CA-A CANCER JOURNAL FOR CLINICIANS, 2011, 61 (06) :409-418
[8]   miR-93-directed downregulation of DAB2 defines a novel oncogenic pathway in lung cancer [J].
Du, L. ;
Zhao, Z. ;
Ma, X. ;
Hsiao, T-H ;
Chen, Y. ;
Young, E. ;
Suraokar, M. ;
Wistuba, I. ;
Minna, J. D. ;
Pertsemlidis, A. .
ONCOGENE, 2014, 33 (34) :4307-4315
[9]   Breast cancer in China [J].
Fan, Lei ;
Strasser-Weippl, Kathrin ;
Li, Jun-Jie ;
St Louis, Jessica ;
Finkelstein, Dianne M. ;
Yu, Ke-Da ;
Chen, Wan-Qing ;
Shao, Zhi-Ming ;
Goss, Paul E. .
LANCET ONCOLOGY, 2014, 15 (07) :E279-E289
[10]   MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-β8 [J].
Fang, L. ;
Deng, Z. ;
Shatseva, T. ;
Yang, J. ;
Peng, C. ;
Du, W. W. ;
Yee, A. J. ;
Ang, L. C. ;
He, C. ;
Shan, S. W. ;
Yang, B. B. .
ONCOGENE, 2011, 30 (07) :806-821