Deregulation of miR-1245b-5p and miR-92a-3p and their potential target gene, GATA3, in epithelial-mesenchymal transition pathway in breast cancer

被引:2
作者
Farsani, Mahtab Yadollahi [1 ]
Farsani, Zeinab Amini [2 ]
Teimuri, Shohreh [3 ]
Kolahdouzan, Mohsen [4 ]
Samani, Reza Eshraghi [4 ]
Teimori, Hossein [2 ]
机构
[1] Shahrekord Univ Med Sci, Sch Adv Technol, Dept Med Biotechnol, Shahrekord, Iran
[2] Shahrekord Univ Med Sci, Basic Hlth Sci Inst, Cellular & Mol Res Ctr, Shahrekord, Iran
[3] Univ Bern, Inst Cell Biol, Bern, Switzerland
[4] Isfahan Univ Med Sci, Sch Med, Dept Surg, Esfahan, Iran
关键词
breast cancer; epithelial-mesenchymal transition; GATA3; MicroRNAs; POOR-PROGNOSIS; EXPRESSION; METASTASIS; RECEPTOR; DIFFERENTIATION; CHEMORESISTANCE; IDENTIFICATION; ASSOCIATION; BIOMARKERS; MICRORNAS;
D O I
10.1002/cnr2.1955
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: MicroRNAs (miRNAs) are small molecules that have prominent roles in tumor development and metastasis and can be used for diagnostic and therapeutic purposes. This study evaluated the expression of miR-92a-3p and miR-1245b-5p and their potential target gene, GATA3 in patients with breast cancer (BC).Materials and Methods: In the search for BC-related microRNAs, miR-124b-5p and miR-92a-3p were selected using Medline through PubMed, miR2disease, miRcancer and miRTarBase. Moreover, target gene GATA3 and their possible interaction in the regulating epithelial-mesenchymal transition (EMT) and invasion was evaluated using in silico tools including miRTarBase, TargetScan, STRING-db, and Cytoscape. The expression level of miR-92a-3p, miR1245b-5p, and GATA3 were assessed on extracted RNAs of tumor and nontumor tissues from 36 patients with BC using qPCR. Additionally, clinical-pathologic characteristics, such as tumor grade, tumor stage, lymph node were taken into consideration and the diagnostic power of these miRNAs and GATA3 was evaluated using the ROC curve analysis.Results: In silico evaluation of miR-92a-3p and miR-1245b-5p supports their potential association with EMT and invasion signaling pathways in BC pathogenesis. Comparing tumor tissues to nontumor tissues, we found a significant downregulation of miR-1245b-5p and miR-92a-3p and upregulation of GATA3. Patients with BC who had decreased miR-92a-3p expression also had higher rates of advanced stage/grade and ER expression, whereas decreased miR-1245b-5p expression was only linked to ER expression and was not associated with lymph node metastasis. The AUC of miR-1245b-5p, miR-92a-3p, and GATA3 using ROC curve was determined 0.6449 (p = .0239), 0.5980 (p = .1526), and 0.7415 (p < .0001), respectively, which showed a significant diagnostic accuracy of miR-1245b-5p and GATA3 between the BC patients and healthy individuals.Conclusion: MiR-1245b-5p, miR-92a-3p, and GATA3 gene contribute to BC pathogenesis and they may be having potential regulatory roles in signaling pathways involved in invasion and EMT pathways in BC pathogenesis, as a result of these findings. More research is needed to determine the regulatory mechanisms that they control.
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页数:15
相关论文
共 62 条
[1]   miR-34a Silences c-SRC to Attenuate Tumor Growth in Triple-Negative Breast Cancer [J].
Adams, Brian D. ;
Wali, Vikram B. ;
Cheng, Christopher J. ;
Inukai, Sachi ;
Booth, Carmen J. ;
Agarwal, Seema ;
Rimm, David L. ;
Gyorffy, Balazs ;
Santarpia, Libero ;
Pusztai, Lajos ;
Saltzman, W. Mark ;
Slack, Frank J. .
CANCER RESEARCH, 2016, 76 (04) :927-939
[2]   Predicting effective microRNA target sites in mammalian mRNAs [J].
Agarwal, Vikram ;
Bell, George W. ;
Nam, Jin-Wu ;
Bartel, David P. .
ELIFE, 2015, 4
[3]   Prediction and analysis of microRNAs involved in COVID-19 inflammatory processes associated with the NF-kB and JAK/STAT signaling pathways [J].
Amini-Farsani, Zeinab ;
Yadollahi-Farsani, Mahtab ;
Arab, Samaneh ;
Forouzanfar, Fatemeh ;
Yadollahi, Mitra ;
Asgharzade, Samira .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2021, 100
[4]   The impact of miR-183/182/96 gene regulation on the maturation, survival, and function of photoreceptor cells in the retina [J].
Amini-Farsani, Zeinab ;
Asgharzade, Samira .
JOURNAL OF COMPARATIVE NEUROLOGY, 2020, 528 (09) :1616-1625
[5]   MiR-221/222 promote chemoresistance to cisplatin in ovarian cancer cells by targeting PTEN/PI3K/AKT signaling pathway [J].
Amini-Farsani, Zeinab ;
Sangtarash, Mohammad Hossein ;
Shamsara, Mehdi ;
Teimori, Hossein .
CYTOTECHNOLOGY, 2018, 70 (01) :203-213
[6]   Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation [J].
Asselin-Labat, Marie-Liesse ;
Sutherland, Kate D. ;
Barker, Holly ;
Thomas, Richard ;
Shackleton, Mark ;
Forrest, Natasha C. ;
Hartley, Lynne ;
Robb, Lorraine ;
Grosveld, Frank G. ;
van der Wees, Jacqueline ;
Lindeman, Geoffrey J. ;
Visvader, Jane E. .
NATURE CELL BIOLOGY, 2007, 9 (02) :201-U103
[7]  
Carter D, 2014, AM J NURS, V114, P17, DOI 10.1097/01.NAJ.0000443762.89516.81
[8]   Gene expression profiling of breast cell lines identifies potential new basal markers [J].
Charafe-Jauffret, E ;
Ginestier, C ;
Monville, F ;
Finetti, P ;
Adélaïde, J ;
Cervera, N ;
Fekairi, S ;
Xerri, L ;
Jacquemier, J ;
Birnbaum, D ;
Bertucci, F .
ONCOGENE, 2006, 25 (15) :2273-2284
[9]   miRTarBase update 2018: a resource for experimentally validated microRNA-target interactions [J].
Chou, Chih-Hung ;
Shrestha, Sirjana ;
Yang, Chi-Dung ;
Chang, Nai-Wen ;
Lin, Yu-Ling ;
Liao, Kuang-Wen ;
Huang, Wei-Chi ;
Sun, Ting-Hsuan ;
Tu, Siang-Jyun ;
Lee, Wei-Hsiang ;
Chiew, Men-Yee ;
Tai, Chun-San ;
Wei, Ting-Yen ;
Tsai, Tzi-Ren ;
Huang, Hsin-Tzu ;
Wang, Chung-Yu ;
Wu, Hsin-Yi ;
Ho, Shu-Yi ;
Chen, Pin-Rong ;
Chuang, Cheng-Hsun ;
Hsieh, Pei-Jung ;
Wu, Yi-Shin ;
Chen, Wen-Liang ;
Li, Meng-Ju ;
Wu, Yu-Chun ;
Huang, Xin-Yi ;
Ng, Fung Ling ;
Buddhakosai, Waradee ;
Huang, Pei-Chun ;
Lan, Kuan-Chun ;
Huang, Chia-Yen ;
Weng, Shun-Long ;
Cheng, Yeong-Nan ;
Liang, Chao ;
Hsu, Wen-Lian ;
Huang, Hsien-Da .
NUCLEIC ACIDS RESEARCH, 2018, 46 (D1) :D296-D302
[10]   Expression of GATA3 in MDA-MB-231 Triple-negative Breast Cancer Cells Induces a Growth Inhibitory Response to TGFβ [J].
Chu, Isabel M. ;
Lai, Wei-Chu ;
Aprelikova, Olga ;
El Touny, Lara H. ;
Kouros-Mehr, Hosein ;
Green, Jeffrey E. .
PLOS ONE, 2013, 8 (04)