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miR-142-3p as tumor suppressor miRNA in the regulation of tumorigenicity, invasion and migration of human breast cancer by targeting Bach-1 expression
- Source :
- Mansoori, B, Mohammadi, A, Ghasabi, M, Shirjang, S, Dehghan, R, Montazeri, V, Holmskov, U, Kazemi, T, Duijf, P, Gjerstorff, M & Baradaran, B 2019, ' miR-142-3p as tumor suppressor miRNA in the regulation of tumorigenicity, invasion and migration of human breast cancer by targeting Bach-1 expression ', Journal of Cellular Physiology, vol. 234, no. 6, pp. 9816-9825 . https://doi.org/10.1002/jcp.27670
- Publication Year :
- 2019
- Publisher :
- US : John Wiley & Sons, 2019.
-
Abstract
- Background: Breast cancer is the most common type of cancer among women, and despite improved treatments, it remains a major challenge. However, improved mechanistic insight may lead to novel therapeutic strategies. miR‐142‐3p belongs to the miR‐142 family and is involved in pathogenesis and metastasis of various types of malignancies by targeting several important messenger RNAs (mRNAs) includingBach‐1. This is especially true for breast cancer, where Bach‐1 is involved in the metastatic spread by deregulation of metastasis‐associated genes. Methods: In this study, we collected 24 breast cancer tissues with 24 adjusted normal tissues to measure the expression levels of miR‐142‐3p and Bach‐1mRNAusingquantitative reverse‐transcription polymerase chain reaction (qRT‐PCR) and IHC. miR‐142‐3p targeting of Bach‐1 expression in MCF‐7andMDA‐MB‐468 breast cancer cells was evaluated using bioinformatics, qRT‐PCR and western blot analyses. The cellular proliferation, invasion, and migration were assessed by MTT, transwell matrigel and wound healing assay and the EMT‐associated proteins C‐X‐C chemokine receptor type 4 (CXCR‐4), matrix metalloproteinase‐9 (MMP9), and vascular endothelial growth factor receptor(VEGFR) were analyzed by western blot analysis. Also, the expression levels of tumor suppressors including miR‐330, miR‐145, and miR‐34a were estimated by qRT‐PCR. Results: Analysis of paired specimens of primary malignant and normal tissues showed that miR‐142‐3p was downregulated, while Bach‐1 mRNA and protein both were overexpressed in the breast cancer tumors. This inverse relationship was confirmed by cell line experiments demonstrating that miR‐142‐3p expression reduced Bach‐1 mRNA levels. Furthermore, replacement of miR‐142‐3p could inhibit the proliferation, invasion, and migration in breast cancer potentially by targeting ofBach‐1 mRNA and subsequent inhibition of CXCR4, MMP9, and VEGFR protein expressions. In addition, induction of miR‐142‐3p could upregulate tumor suppressor miRNAs, including miR‐330, miR‐145, and miR34a. Conclusion: For the first time, our results revealed that miR‐142‐3p could targetBach‐1in breast cancer cells leading to the reduction of EMT‐related proteins and reduced cell proliferation, invasion, and migration. The results also demonstrated that miR‐142‐3p could regulate important tumor suppressor miRNAs in breast cancer cells. In conclusion, our results suggest that miR‐142‐3p could be a good candidate for the targeted therapy of breast cancer, especially for the invasive type. Refereed/Peer-reviewed
- Subjects :
- 0301 basic medicine
Physiology
Carcinogenesis
medicine.medical_treatment
Clinical Biochemistry
miR-142-3p
Down-Regulation
Breast Neoplasms
Biology
MMP9
migration
CXCR4
Bach-1
Metastasis
Targeted therapy
03 medical and health sciences
0302 clinical medicine
Breast cancer
breast cancer
Cell Movement
Cell Line, Tumor
microRNA
medicine
Humans
Neoplasm Invasiveness
RNA, Messenger
Cell Proliferation
Matrigel
Cancer
Cell Biology
medicine.disease
invasion
Up-Regulation
Gene Expression Regulation, Neoplastic
MicroRNAs
030104 developmental biology
Basic-Leucine Zipper Transcription Factors
030220 oncology & carcinogenesis
Cancer research
Female
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Mansoori, B, Mohammadi, A, Ghasabi, M, Shirjang, S, Dehghan, R, Montazeri, V, Holmskov, U, Kazemi, T, Duijf, P, Gjerstorff, M & Baradaran, B 2019, ' miR-142-3p as tumor suppressor miRNA in the regulation of tumorigenicity, invasion and migration of human breast cancer by targeting Bach-1 expression ', Journal of Cellular Physiology, vol. 234, no. 6, pp. 9816-9825 . https://doi.org/10.1002/jcp.27670
- Accession number :
- edsair.doi.dedup.....7da364f6977985fd31addb63010696e1