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Long non-coding RNA TPT1-AS1 sensitizes breast cancer cell to paclitaxel and inhibits cell proliferation by miR-3156-5p/caspase 2 axis

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Abstract

Long non-coding RNAs (lncRNAs) are key modulators during cancer progression. Application of using lncRNA expression to evaluate patient prognosis and sensitivity to treatment is highly anticipated, yet the expression and mechanism of many lncRNAs remain unknown. Herein, we projected for the investigation of TPT1-AS1 function in breast cancer. TPT1-AS1 was assessed by bioinformatic analysis of publicly available datasets and quantitative real-time PCR (qRT-PCR). Cell sensitivity to paclitaxel and cell proliferation was measured by flow cytometry and CCK-8. Interaction among TPT1-AS1, microRNA (miRNA, miR)-3156-5p and Caspase 2 (CASP2) was studied by bioinformatic analysis, qRT-PCR, western blot as well as dual luciferase reporter assay. Herein, TPT1-AS1 was significantly diminished in breast cancer from publicly available datasets and our collected samples. In breast cancer cells, TPT1-AS1 overexpression repressed cell proliferation and sensitized breast cancer cells to paclitaxel. RegRNA 2.0 predicted a potential interaction between TPT1-AS1 and miR-3156-5p which was confirmed by qRT-PCR as well as dual luciferase reporter assay. CASP2, a proapoptotic gene, was corroborated to be targeted by miR-3156-5p. Meanwhile, TPT1-AS1 upregulated CASP2 in breast cancer cells, and its biological function was reversed by CASP2 knockdown. Collectively, TPT1-AS1 diminished cell proliferation and sensitized cells to chemotherapy by sponging miR-3156-5p and upregulating CASP2, acting as a biomarker for patients with breast cancer.

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Funding

Current study was funded by Zhejiang Provincial Medical Science and Technology program (Grant no. 2016RCA003) and Zhejiang Science and Technology program (Grant no. 2016C33199).

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Author notes

  1. Yuan Huang and Yabing Zheng contributed equally to the present study.

Authors and Affiliations

  1. Department of Breast Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), No 1, East Banshan Road, Gongshu District, Hangzhou, Zhejiang, 310022, People’s Republic of China

    Yuan Huang, Yabing Zheng, Xiying Shao, Lei Shi, Guangliang Li & Ping Huang

  2. Department of Breast Medical Oncology, Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, People’s Republic of China

    Yuan Huang, Yabing Zheng, Xiying Shao, Lei Shi, Guangliang Li & Ping Huang

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  1. Yuan Huang
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  2. Yabing Zheng
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  4. Lei Shi
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Contributions

YH and YZ conceived the study, conducted the experimentations, and prepared the manuscript. XS, LS, GL, and PH carried out the experiments and analyzed the data.

Corresponding author

Correspondence to Yabing Zheng.

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The author(s) declare that they have no conflict of interests.

Ethics approval and consent to participate

Current study was approved by the Ethic Committee of Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital).

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Written informed consent was obtained from each patient before our study.

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Huang, Y., Zheng, Y., Shao, X. et al. Long non-coding RNA TPT1-AS1 sensitizes breast cancer cell to paclitaxel and inhibits cell proliferation by miR-3156-5p/caspase 2 axis. Human Cell 34, 1244–1254 (2021). https://doi.org/10.1007/s13577-021-00541-z

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  • DOI: https://doi.org/10.1007/s13577-021-00541-z

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