Dataset Information

MicroRNA-762 promotes breast cancer cell proliferation and invasion by targeting IRF7 expression.

ABSTRACT:

Objectives

miRNAs play crucial roles in human tumourigenesis. This study was performed to measure expression and function of miR-762 in breast cancer.

Materials and methods

Expression of miR-762 in breast tissues and cell lines (SK-BR-3, DA-MB-435s, MCF-7 and MDA-MB-231, HBL-100) was measured by using real-time RT-PCR. We restored expression of miR-762 in MCF-7 cells to measure its functional roles. Luciferase assays were performed to reveal the target gene of miR-762.

Results

Expression of miR-762 was high in both breast cancer cell lines and specimens, and its overexpression increased breast cancer cell proliferation and invasion. Interferon regulatory factor 7 (IRF7) is a direct target of miR-762 and overexpression of miR-762 reduced expression of IRF7. Moreover, IRF7 was repressed, its levels inversely correlated to miR-762 expression. IRF7 rescued miR-762-induced cell invasion and proliferation.

Conclusions

These results demonstrate that miR-762 tumour effect was achieved by targeting IRF7 in human breast cancer specimens.

SUBMITTER: Li Y

PROVIDER: S-EPMC6496530 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

microRNA-762 promotes breast cancer cell proliferation and invasion by targeting IRF7 expression.

Li Yongping Y Huang Ruixue R Wang Ling L Hao Junsheng J Zhang Qiong Q Ling Rui R Yun Jun J

Cell proliferation 20151102 6

<h4>Objectives</h4>miRNAs play crucial roles in human tumourigenesis. This study was performed to measure expression and function of miR-762 in breast cancer.<h4>Materials and methods</h4>Expression of miR-762 in breast tissues and cell lines (SK-BR-3, DA-MB-435s, MCF-7 and MDA-MB-231, HBL-100) was measured by using real-time RT-PCR. We restored expression of miR-762 in MCF-7 cells to measure its functional roles. Luciferase assays were performed to reveal the target gene of miR-762.<h4>Results< ...[more]

PMID: 26597380

Similar Datasets

Project description:MicroRNAs (miRNAs/miRs) are highly conserved single-stranded small non-coding RNAs, which are involved in the physiological and pathological processes of breast cancer, and affect the prognosis of patients with breast cancer. The present study used the Gene Expression Omnibus (GEO)2R tool to detect miR-100 expression in breast cancer tissues obtained from GEO breast cancer-related datasets. Bioinformatics analysis revealed that miR-100 expression was downregulated in different stages, grades and lymph node metastasis stages of breast cancer, and patients with high miR-100 expression had a more favorable prognosis. Based on these analyses, Cell Counting Kit-8, wound healing and Transwell assays were performed, and the results demonstrated that overexpression of miR-100 inhibited the proliferation, migration and invasion of breast cancer cells. To verify the tumor-suppressive effect of miR-100 in breast cancer, the LinkedOmics and PITA databases were used to assess the association between miR-100 and forkhead box A1 (FOXA1). The results demonstrated that miR-100 had binding sites within the FOXA1 gene, and FOXA1 expression was negatively associated with miR-100 expression in breast cancer tissues. Similarly, a negative association was observed between miR-100 and FOXA1 expression, using the StarBase V3.0 database. The association between miR-100 and FOXA1 was further verified via reverse transcription-quantitative PCR and western blot analyses, and the dual-luciferase reporter assay. The results demonstrated that miR-100 targeted the 3'-untranslated region of FOXA1 in breast cancer cells. Furthermore, rescue experiments were performed to confirm whether miR-100 exerts its antitumor effects by regulating FOXA1. The results demonstrated that overexpression of FOXA1 promoted the proliferation, migration and invasion of breast cancer cells; thus, the antitumor effects of miR-100 in breast cancer were reversed following overexpression of FOXA1. Taken together, the results of the present study suggest that miR-100 inhibits the proliferation, migration and invasion of breast cancer cells by targeting FOXA1 expression. These results may provide a novel insight and an experimental basis for identifying effective therapeutic targets of high specificity for breast cancer.

Project description:BackgroundBreast 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.MethodsqRT-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.ResultsPlasma 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.ConclusionsThese 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 registrationRetrospectively registered.