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MicroRNA‑606 inhibits the growth and metastasis of triple‑negative breast cancer by targeting Stanniocalcin 1.

ABSTRACT: Triple‑negative breast cancer (TNBC) is associated with a poor prognosis; however, treatments for TNBC are limited, with poor outcomes. MicroRNAs (miRNAs/miRs) are small non‑coding RNA molecules that are able to regulate gene expression. The present study aimed to identify differentially expressed miRNAs in patients with breast cancer, and to investigate the functional role of the identified miRNA targets and their effects in vitro and in vivo. Transfection with miR‑606 suppressed TNBC cell proliferation, migration, invasion and tumor sphere‑forming ability, as determined using trypan blue, Transwell and sphere formation assays. Moreover, miR‑606 induced the apoptosis of TNBC cells, as determined by flow cytometric analysis. Furthermore, intratumoral injections of miR‑606 mimics suppressed tumor growth in MDA‑MB‑231 xenografts. In addition, MDA‑MB‑231 cells transfected with miR‑606 mimics exhibited decreased lung metastatic nodules in a mouse tail vein injection model. Notably, miR‑606 and STC1 expression had opposing effects on the overall survival of patients with TNBC. The results of the present study suggested a novel tumor suppressor function for miR‑606 in TNBC, thus indicating its potential application in the development of anticancer miRNA therapeutics.

SUBMITTER: Choi S

PROVIDER: S-EPMC10688449 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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MicroRNA‑606 inhibits the growth and metastasis of triple‑negative breast cancer by targeting Stanniocalcin 1.

Choi Sujin S An Hyun-Ju HJ Yeo Hyun Jeong HJ Sung Min-Ji MJ Oh Jisu J Lee Kwanbum K Lee Seung Ah SA Kim Seung Ki SK Kim Junhan J Kim Isaac I Lee Soonchul S

Oncology reports 20231117 1

Triple‑negative breast cancer (TNBC) is associated with a poor prognosis; however, treatments for TNBC are limited, with poor outcomes. MicroRNAs (miRNAs/miRs) are small non‑coding RNA molecules that are able to regulate gene expression. The present study aimed to identify differentially expressed miRNAs in patients with breast cancer, and to investigate the functional role of the identified miRNA targets and their effects <i>in vitro</i> and <i>in vivo</i>. Transfection with miR‑606 suppressed ...[more]

PMID: 37975233

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Project description:BackgroundThe triple-negative subtype of breast cancer is particularly challenging to treat due to its aggressiveness with a high risk of brain metastasis, and the lack of effective targeted therapies. Tubulin beta 2B class IIb (TUBB2B), a β-tubulin isoform regulating axon guidance during embryonic development, was found to be overexpressed in various types of cancers including triple-negative breast cancer (TNBC). However, its functional roles in breast cancer or metastasis remain unclear.MethodsTo identify TUBB2B as a novel molecular target in TNBC, we performed bioinformatics analysis to assess the association of TUBB2B expression and survival of patients. RNAscope in situ hybridization was used to examine TUBB2B expression in clinical breast tumor samples. The effect of TUBB2B knockdown on TNBC growth and brain metastasis colonization was evaluated by in vitro and in vivo assays. Mass spectrometry (MS) and biochemical experiments were performed to explore the underlying mechanisms. Preclinical efficacy of targeting TUBB2B was determined in xenograft studies using the siRNA-gold nanoparticle (siRNA-AuNP) approach.ResultsTUBB2B, but not other β-tubulin isoforms, is frequently overexpressed in TNBC primary tumors as well as brain metastases. We also find that upregulation of TUBB2B is associated with poor prognosis in breast cancer patients. Silencing TUBB2B induces tumor cell death and inhibits the outgrowth of brain metastasis. Mechanistically, we identify eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) as a novel interacting partner of TUBB2B, revealing a previously unexplored role of TUBB2B in translational regulation. In line with its neural-related functions, TUBB2B overexpression in TNBC cells activates astrocytes, which in turn upregulate TUBB2B in tumor cells. These findings suggest a feed-forward interaction between TUBB2B in TNBC cells and astrocytes that promotes brain metastatic colonization. Furthermore, we demonstrate the potent inhibition of TNBC xenograft growth as well as brain metastatic colonization using TUBB2B siRNA-AuNP treatment, indicating potential clinical applications of targeting TUBB2B for TNBC.ConclusionsTUBB2B is a novel TNBC gene that plays a key role in promoting tumor cell survival and brain metastatic colonization, and can be targeted by siRNA-AuNPs as a treatment strategy.

Dataset Information

MicroRNA‑606 inhibits the growth and metastasis of triple‑negative breast cancer by targeting Stanniocalcin 1.

Publications

MicroRNA‑606 inhibits the growth and metastasis of triple‑negative breast cancer by targeting Stanniocalcin 1.

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