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microRNA-944 inhibits breast cancer cell proliferation and promotes cell apoptosis by reducing SPP1 through inactivating the PI3K/Akt pathway

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Abstract

Breast cancer is a common malignancy in women with poor prognosis. This study aimed to investigate the molecular mechanism of microRNA-944 (miR-944) mediated secreted phosphoprotein-1 (SPP1) in breast cancer progression and its regulatory effect on the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Differential gene analysis was performed to identify key genes associated with breast cancer development by screening breast cancer-related microarray data. The expression of miR-944 and SPP1 and their relationship were determined in clinical samples and cells. sh-SPP1, oe-SPP1, LY294002 or miR-944 mimic were transfected into MCF-7 cells to investigate the role of miR-944 mediated SPP1 in breast cancer development and its regulatory effect on the PI3K/Akt pathway. Finally, the tumorigenicity of breast cancer cells was observed in nude mice. Through bioinformatics analysis, we identified SPP1 as a key gene in breast cancer, and miR-944 as an upstream miRNA of SPP1. In breast cancer tissues and cells, the expression of miR-944 was decreased while that of SPP1 was increased. miR-944 negatively regulated the expression of SPP1. In breast cancer cells, SPP1 activated the PI3K/Akt pathway to promote cell proliferation and inhibit apoptosis. In vitro cell experiments showed that the downregulation of miR-944 promoted the high expression of SPP1, which then activated the PI3K/Akt signaling pathway, promoting breast cancer cell proliferation. In vivo experiments further confirmed the anti-cancer role of miR-944 mediated SPP1 in breast cancer. Our study highlights the role of miR-944 mediated SPP1 in inhibiting breast cancer progression by blocking the PI3K/Akt pathway.

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Data Availability

The data underlying this article will be shared on reasonable request to the corresponding author.

Abbreviations

SPP1:

Secreted phosphoprotein-1

PI3K:

Phosphoinositide 3-kinase

OS:

Overall survival, BRCA, breast cancer, DEGs, differentially expressed genes

PPI:

Protein-protein interaction

GSEA:

Gene set enrichment analysis

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Authors and Affiliations

  1. Department of Thyroid and Breast Surgery, the People’s Hospital of Liaoning Province, Shengyang, Liaoning, 110001, China

    Ying Zhang

  2. Department of General Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China

    Shan Li

  3. Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning, 110022, China

    Xiangguo Cui

  4. Department of Anesthesiology, the First Hospital of China Medical University, No.155, Nanjing North Street, Heping District, Shengyang, Liaoning, 110001, China

    Yiliang Wang

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Contributions

Conceptualization, Ying Zhang, Shan Li, Xiangguo Cui, Yiliang Wang; Formal analysis, Ying Zhang, Shan Li; Investigation, Ying Zhang, Shan Li; Methodology, Ying Zhang, Shan Li; Project administration, Ying Zhang, Shan Li, Xiangguo Cui, Yiliang Wang; Resources, Xiangguo Cui, Yiliang Wang; Supervision, Xiangguo Cui, Yiliang Wang; Writing – original draft, Ying Zhang, Shan Li; Writing – review & editing, Xiangguo Cui, Yiliang Wang. All authors have read and approved the final submitted manuscript.

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Correspondence to Xiangguo Cui or Yiliang Wang.

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This study was approved by the clinical ethics committee of the First Hospital of China Medical University, in strict accordance with the Declaration of Helsinki. All patients signed the informed consent form. During animal experiments, the principles of completing experiments with the least number of animals and minimizing the pain of experimental animals were strictly obeyed.

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Zhang, Y., Li, S., Cui, X. et al. microRNA-944 inhibits breast cancer cell proliferation and promotes cell apoptosis by reducing SPP1 through inactivating the PI3K/Akt pathway. Apoptosis 28, 1546–1563 (2023). https://doi.org/10.1007/s10495-023-01870-0

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