RETRACTED: MicroRNA-326 Functions as a Tumor Suppressor in Breast Cancer by Targeting ErbB/PI3K Signaling Pathway (Retracted Article)

被引:47
作者
Ghaemi, Zahra [1 ]
Soltani, Bahram Mohammad [1 ]
Mowla, Seyed Javad [1 ]
机构
[1] Tarbiat Modares Univ, Fac Biol Sci, Dept Genet, Tehran, Iran
关键词
ErbB/PI3K signaling pathway; miR-326; breast cancer; tumor suppressor; microRNA; ERBB RECEPTORS; PI3K PATHWAY; CELL-PROLIFERATION; RESISTANCE; APOPTOSIS; PROGRESSION; BIOGENESIS; ACTIVATION; EXPRESSION; MECHANISM;
D O I
10.3389/fonc.2019.00653
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Breast cancer represents the most common malignancy in women worldwide and the ErbB/PI3K pathway has been found to play a crucial role in regulation of the cancer cell growth. MicroRNAs have been implicated in regulating diverse cellular pathways and therefore, understanding the link between the regulatory microRNAs and the ErbB/PI3K signaling pathway could potentially be helpful for breast cancer prevention and treatment. The aim of this study is to examine the regulatory effect of miR-326 on ErbB/PI3K signaling pathway in breast cancer development and progression. The results of qRT-PCR, RNA seq, and array data indicated that miR-326 was remarkably down-regulated in breast tumor tissues and correlated with poor survival outcome. Importantly, very low levels of miR-326 expression were found in aggressive breast cells compared to less-aggressive cell types. Mechanistically, a gene network including EGFR, ErbB2, ErbB3, AKT1, AKT2, and AKT3 targeted by miR-326, thereby providing suppression of ErbB/PI3K pathway, detected by RT-qPCR, and dual luciferase assay. In addition, Western blot analysis revealed that miR-326 upregulation decreased PI3K signaling activity by decreasing total AKT and p-AKT protein level in SKBR3 cell lines. Interestingly, up regulation of ErbB2 rescued the effect of miR-326 on miR-326 target genes. Further functional assays demonstrated that up regulation of miR-326 significantly suppressed cell growth as evidenced by cell cycle, cell cycle associated genes expression, colony formation and MTT assays and induced apoptosis, detected by Annexin V-PI. In addition, EMT markers RT-qPCR, scratch, and Transwell assays showed inhibited cellular migration and invasion following miR-326 upregulation. Altogether, our results revealed that miR-326 play a tumor-suppressive role in breast cancer through inhibiting ErbB/PI3K pathway and miR-326 may serve as a potential therapeutic target for the treatment of patients with breast cancer.
引用
收藏
页数:12
相关论文
共 54 条
[1]   Predicting effective microRNA target sites in mammalian mRNAs [J].
Agarwal, Vikram ;
Bell, George W. ;
Nam, Jin-Wu ;
Bartel, David P. .
ELIFE, 2015, 4
[2]   ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics [J].
Arteaga, Carlos L. ;
Engelman, Jeffrey A. .
CANCER CELL, 2014, 25 (03) :282-303
[3]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[4]   Novel anticancer targets: revisiting ERBB2 and discovering ERBB3 [J].
Baselga, Jose ;
Swain, Sandra M. .
NATURE REVIEWS CANCER, 2009, 9 (07) :463-475
[5]   A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer [J].
Berns, Katrien ;
Horlings, Hugo M. ;
Hennessy, Bryan T. ;
Madiredjo, Mandy ;
Hijmans, E. Marielle ;
Beelen, Karin ;
Linn, Sabine C. ;
Gonzalez-Angulo, Ana Maria ;
Stemke-Hale, Katherine ;
Hauptmann, Michael ;
Beijersbergen, Roderick L. ;
Mills, Gordon B. ;
de Vijver, Marc J. van ;
Bernards, Rene .
CANCER CELL, 2007, 12 (04) :395-402
[6]   The microRNA.org resource: targets and expression [J].
Betel, Doron ;
Wilson, Manda ;
Gabow, Aaron ;
Marks, Debora S. ;
Sander, Chris .
NUCLEIC ACIDS RESEARCH, 2008, 36 :D149-D153
[7]   MiR-326 is a diagnostic biomarker and regulates cell survival and apoptosis by targeting Bcl-2 in osteosarcoma [J].
Cao, Lei ;
Wang, Jiandong ;
Wang, Qiugen .
BIOMEDICINE & PHARMACOTHERAPY, 2016, 84 :828-835
[8]   Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy [J].
Chang, F ;
Lee, JT ;
Navolanic, PM ;
Steelman, LS ;
Shelton, JG ;
Blalock, WL ;
Franklin, RA ;
McCubrey, JA .
LEUKEMIA, 2003, 17 (03) :590-603
[9]   Twist transcriptionally up-regulates AKT2 in breast cancer cells leading to increased migration, invasion, and resistance to paclitaxel [J].
Cheng, George Z. ;
Chan, Joseph ;
Wang, Qi ;
Zhang, Weizhou ;
Sun, Calvin D. ;
Wang, Lu-Hai .
CANCER RESEARCH, 2007, 67 (05) :1979-1987
[10]   MicroRNAs: Potential biomarkers for cancer diagnosis, prognosis and targets for therapy [J].
Cho, William C. S. .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2010, 42 (08) :1273-1281