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microRNA-21 promotes breast cancer proliferation and metastasis by targeting LZTFL1
- Source :
- BMC Cancer, BMC Cancer, Vol 19, Iss 1, Pp 1-13 (2019)
- Publication Year :
- 2018
-
Abstract
- Background Breast cancer is the most common cancer type in female. As microRNAs play vital role in breast cancer, this study aimed to explore the molecular mechanism and clinical value of miR-21 in breast cancer. Methods qRT-PCR was performed to detect miR-21 levels in plasma of 127 healthy controls, 82 benign breast tumor, 252 breast cancer patients, as well as in breast cancer cell lines. Transwell and wound healing assay were used to analyze breast cancer metastasis in response to miR-21 inhibitor. Colony formation and eFluor™ 670 based flow cytometric analysis were used to test breast cancer proliferation following miR-21 inhibitor treatment. Leucine zipper transcription factor-like 1 (LZTFL1), the target gene of miR-21 was predicted by MIRDB, TargetScan 5.1, PicTar and miRanda. Survival analysis of LZTFL1 levels in breast cancer prognosis was estimated with the Kaplan–Meier method by log-rank test according to data from the Cancer Genome Atlas. Luciferase activity assay was performed to confirm the regulation of miR-21 on LZTFL1. LZTFL1 siRNA and miR-21 inhibitor were co-transfected to breast cancer cells, then cell proliferation, migration and epithelial–mesenchymal transition (EMT) makers were tested. BALB/c nude mice were injected in situ with Hs578T cells stably overexpressing miR-21. Breast tumor growth, metastasis and the expression of EMT markers or LZTFL1 were detected in vivo. Results Plasma miR-21 levels were elevated in breast cancer patients compared with healthy controls and benign breast tumor patients, and the miR-21 levels were significantly decreased after surgery comparing with pre operation in 44 patients. Inhibition of miR-21 suppressed cell proliferation and metastasis in breast cancer cells. LZTFL1 was identified as a novel target gene of miR-21. Knockdown of LZTFL1 overcame the suppression of miR-21 inhibitor on cell proliferation, metastasis and the expression of EMT markers in breast cancer cells. miR-21 overexpression promoted breast cancer cell proliferation and metastasis in vivo. Conclusions These results indicate that plasma miR-21 level is a crucial biomarker for breast cancer diagnosis and targeting miR-21–LZTFL1–EMT axis might be a promising strategy in breast cancer therapy. Trial registration Retrospectively registered. Electronic supplementary material The online version of this article (10.1186/s12885-019-5951-3) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
Cancer Research
Kaplan-Meier Estimate
Metastasis
Mice
0302 clinical medicine
Breast cancer
Surgical oncology
skin and connective tissue diseases
beta Catenin
Gene knockdown
Mice, Inbred BALB C
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Tumor Burden
Survival Rate
Oncology
030220 oncology & carcinogenesis
MCF-7 Cells
Heterografts
Female
Research Article
Epithelial-Mesenchymal Transition
Mice, Nude
Breast Neoplasms
Transfection
lcsh:RC254-282
03 medical and health sciences
In vivo
microRNA
Genetics
medicine
Biomarkers, Tumor
Animals
Humans
Epithelial–mesenchymal transition
Cell Proliferation
Epithelial to mesenchymal transition
Cell growth
business.industry
Leucine zipper transcription factor-like 1
medicine.disease
MicroRNAs
030104 developmental biology
HEK293 Cells
Cancer research
business
Transcription Factors
microRNA-21
Subjects
Details
- ISSN :
- 14712407
- Volume :
- 19
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- BMC cancer
- Accession number :
- edsair.doi.dedup.....31fd3b96a425f339d67346603688331f