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SOX2-OT induced by PAI-1 promotes triple-negative breast cancer cells metastasis by sponging miR-942-5p and activating PI3K/Akt signaling

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Abstract

Triple-negative breast cancer (TNBC) has an aggressive biological behavior and poor outcome. Our published study showed that PAI-1 could induce the migration and metastasis of TNBC cells. However, the underlying mechanism by which PAI-1 regulates TNBC metastasis has not been addressed. Here, we demonstrated that PAI-1 is high expressed in TNBC and promotes TNBC cells tumorigenesis. Using microarray analysis of lncRNA expression profiles, we identified a lncRNA SOX2-OT, which is induced by PAI-1 and could function as an oncogenic lncRNA in TNBC. Mechanistic analysis demonstrated that SOX2-OT acts as a molecular sponge for miR-942-5p to regulate the expression of PIK3CA, ultimately leading to activating PI3K/Akt signaling pathway and promoting TNBC metastasis. Taken together, our findings suggest that SOX2-OT regulates PAI-1-induced TNBC cell metastasis through miR-942-5p/PIK3CA signaling and illustrate the great potential of developing new SOX2-OT-targeting therapy for TNBC patients.

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Availability of data and material

All data and materials in this study are available upon request.

Abbreviations

TNBC:

Triple-negative breast cancer

ER:

Estrogen receptor

PR:

Progesterone receptor

HER-2:

Human epidermal growth factor receptor 2

LEC:

Lymphatic vessel endothelial cell

LV:

Lymphatic vessel

EC:

Endothelial cell

EMT:

Epithelial–mesenchymal transition

LncRNA:

Long non-coding RNA

ceRNA:

Competing endogenous RNA

RIP:

RNA immunoprecipitation

GSEA:

Gene set enrichment analysis

OS:

Overall survival

RFS:

Relapse-free survival

DMFS:

Distant metastasis-free survival

BMSC:

Bone mesenchymal stem cell

IHC:

Immunohistochemistry

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Funding

This research was supported by National Natural Science Foundation of China (No. 81802667, 81773102), Natural Science Foundation of Jiangsu Province (BK20180133), Nanjing Outstanding Youth Fund (No. JQX20009), Key International Cooperation of the National Natural Science Foundation of China (No. 81920108029), and Key Foundation for Social Development Project of the Jiangsu Province, China (BE2021741).

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Author notes

  1. Wenwen Zhang, Shuofei Yang and Datian Chen have contributed equally to this work.

Authors and Affiliations

  1. Department of Oncology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, China

    Wenwen Zhang, Daolu Yuwen, Juan Zhang & Xiaowei Wei

  2. Department of Vascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China

    Shuofei Yang

  3. Department of Oncology, Haimen People’s Hospital, Nantong University, Nantong, China

    Datian Chen

  4. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China

    Xin Han

  5. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China

    Xiaoxiang Guan

  6. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, China

    Xiaoxiang Guan

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  1. Wenwen Zhang
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  2. Shuofei Yang
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  3. Datian Chen
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  5. Juan Zhang
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  7. Xin Han
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Contributions

WZ and XG designed the study. WZ, SY, DC, DY, JZ, XH and XW performed the experiments and acquired the data. WZ, SY, DC, XH and XW analyzed the data. WZ, SY, XH and XG contributed to discussion and writing of the manuscript.

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Correspondence to Wenwen Zhang, Xin Han or Xiaoxiang Guan.

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Studies were performed, according to the ethical guidelines of the Helsinki Declaration and were approved by the Clinical Research Ethics Committee of Nanjing First Hospital.

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Zhang, W., Yang, S., Chen, D. et al. SOX2-OT induced by PAI-1 promotes triple-negative breast cancer cells metastasis by sponging miR-942-5p and activating PI3K/Akt signaling. Cell. Mol. Life Sci. 79, 59 (2022). https://doi.org/10.1007/s00018-021-04120-1

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