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Expression and clinical significance of hypoxia-induced long non-coding RNA TCONS_I2_00001955 in breast cancer

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Abstract

Background

Long non-coding RNAs (lncRNAs) have been found to play important roles in occurrence, development, and metastasis of various tumors. We aimed to screen long non-coding RNAs (lncRNAs) that promote invasion and metastasis of breast cancer cells under hypoxia, and investigate the relationship between lncRNA expression and clinicopathological features and prognosis in invasive breast cancer.

Methods

LncRNA microarray was used to screen the differentially expressed lncRNAs in MCF7, MDA-MB-231, and SKBR3 breast cancer cell lines cultured under normoxia and hypoxia, respectively. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to verify the microarray results. CCK8 and Transwell experiments were performed to identify the lncRNA that promote proliferation, migration, and invasion of breast cancer cells. Expression of the lncRNA and HIF-1α in invasive breast cancer was detected by RNAscope and immunohistochemistry, respectively. Correlation between the lncRNA expression and baseline characteristics was analyzed. Prognostic value of the lncRNA was evaluated using univariate and multivariate Cox regression.

Results

Expression of lncRNA TCONS_I2_00001955 in all the three breast cancer cells was increased under hypoxia. Overexpression of TCONS_I2_00001955 significantly enhanced proliferation, migration, and invasion of SKBR3 cells. Positive expression of TCONS_I2_00001955 was associated with recurrence, metastasis, and high expression of HIF-1α (P < 0.05), and it was an independent risk factor for poor disease-free survival of breast cancer.

Conclusion

Hypoxia-induced lncRNA TCONS_I2_00001955 was associated with aggressive feature and poor prognosis of breast cancer.

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Data availability

The data of this manuscript are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81502271), and the Medical Scientific Research Foundation of Guangdong Province, China (No. A2020485).

Author information

Author notes

  1. Jie-Yin Zhuang, Ze-Nan Huang, and Zi-** Weng have contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, China

    Jie-Yin Zhuang, Meng-Meng Liu & Min Dong

  2. Department of Medical Oncology, The Cancer Hospital of Shantou University Medical College, Shantou, China

    Jie-Yin Zhuang

  3. Breast Cancer Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

    Ze-Nan Huang

  4. Department of Pathology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

    Zi-** Weng, **ang-Qi Huang, Dan He & Chun-Kui Shao

  5. Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China

    Meng-Meng Liu

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Contributions

MD conceived and designed the experiments. ZNH collected and followed up cases. JYZ, MML, XQH, ZJW and DH participated in the experimental process. ZJW and JYZ analyzed the data. JYZ and MD drafted the manuscript. CKS revised articles. All authors contributed to the article and approved the submitted version.

Corresponding author

Correspondence to Min Dong.

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All authors have no conflicts of interest to declare.

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This study was approved by the Third Affiliated Hospital of Sun Yat-sen University and Institute and complied with the Helsinki declaration. Written informed consent was obtained from all participants.

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Zhuang, JY., Huang, ZN., Weng, ZJ. et al. Expression and clinical significance of hypoxia-induced long non-coding RNA TCONS_I2_00001955 in breast cancer. Breast Cancer 31, 317–328 (2024). https://doi.org/10.1007/s12282-023-01540-8

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  • DOI: https://doi.org/10.1007/s12282-023-01540-8

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