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Upregulation of microRNA?1 inhibits proliferation and metastasis of breast cancer.

ABSTRACT: Recent studies have shown that microRNAs (miRs) play a key role in the regulation of cancer development. In the present study, reverse transcription?quantitative PCR was used to detect the expression of miR?1 in breast cancer and adjacent tissues, and survival analysis was performed to compare the low?expression groups with the Kaplan-Meier method. Overexpression of miR?1 was used to observe the effects on the proliferation, migration and invasion of breast cancer cells in vitro and in vivo. Moreover, Bcl?2 expression was measured by western blotting and luciferase assays after the overexpression of miR?1. The present study reported that miR?1 is expressed at low levels in breast cancer and that cell proliferation, migration and invasion are inhibited in miR?1?overexpressing cells. Enhanced miR?1 expression can also increase cell apoptosis. The present study also demonstrated that Bcl?2 is a potential target of miR?1. In vivo studies indicate that overexpression of miR?1 decreases tumor volume and weight in nude mice. The data from the present study demonstrated for the first time that overexpression of miR?1 increases the sensitivity of breast cancer cells to paclitaxel and cisplatin. The present study provided new evidence for the important role of miR?1 in the tumorigenesis and drug sensitivity of breast cancer.

SUBMITTER: Peng J

PROVIDER: S-EPMC7248535 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Upregulation of microRNA‑1 inhibits proliferation and metastasis of breast cancer.

Peng Jing J Yuan Chenwei C Wu Ziping Z Wang Yan Y Yin Wenjin W Lin Yanping Y Zhou Liheng L Lu Jinsong J

Molecular medicine reports 20200504 1

Recent studies have shown that microRNAs (miRs) play a key role in the regulation of cancer development. In the present study, reverse transcription‑quantitative PCR was used to detect the expression of miR‑1 in breast cancer and adjacent tissues, and survival analysis was performed to compare the low‑expression groups with the Kaplan-Meier method. Overexpression of miR‑1 was used to observe the effects on the proliferation, migration and invasion of breast cancer cells in vitro and in vivo. Mor ...[more]

PMID: 32377691

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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.

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Upregulation of microRNA?1 inhibits proliferation and metastasis of breast cancer.

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Upregulation of microRNA‑1 inhibits proliferation and metastasis of breast cancer.

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