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Tanshinone IIA (TSIIA) represses the progression of non-small cell lung cancer by the circ_0020123/miR-1299/HMGB3 pathway

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Abstract

Tanshinone IIA (TSIIA), a multi-pharmaceutical compound, has been demonstrated to have anti-tumor properties. This study explores the potential regulatory mechanism of TSIIA on non-small cell lung cancer (NSCLC) progression. The cytotoxicity of TSIIA was evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) and LDH (lactate dehydrogenase) assays. Expression levels of circ_0020123 (hsa_circ_0020123) and microRNA-1299 (miR-1299) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, migration, invasion, and apoptosis were analyzed by MTT, colony formation, transwell, wound-healing, or flow cytometry assays. The relationship between miR-1299 and circ_0020123 or HMGB3 (high mobility group box 3) was verified by the dual-luciferase reporter and/or RNA immunoprecipitation (RIP) assays. Protein level of HMGB3 was measured by western blotting. The relationship between TSIIA and circ_0020123 was confirmed by xenograft assay. TSIIA reduced xenograft tumor growth in vivo and repressed proliferation, migration, invasion, and facilitated apoptosis of NSCLC cells in vitro. TSIIA reduced circ_0020123 and HMGB3 expression, whereas elevated miR-1299 expression in NSCLC cells. Circ_0020123 knockdown enhanced the repressive influence of TSIIA treatment on the malignancy of NSCLC cells in vitro and in vivo. Circ_0020123 sponged miR-1299 to regulate HMGB3 expression under TSIIA treatment. MiR-1299 inhibitor reversed circ_0020123 knockdown-mediated influence on malignant behaviors of NSCLC cells under TSIIA treatment. HMGB3 elevation offset the suppressive impact of miR-1299 mimic on the malignancy of NSCLC cells under TSIIA treatment. TSIIA curbed NSCLC progression by the circ_0020123/miR-1299/HMGB3 axis, manifesting that the TSIIA/circ_0020123/miR-1299/HMG regulatory network might be a potential treatment strategy for NSCLC.

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Data availability

The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.

Abbreviations

TSIIA:

Tanshinone IIA

NSCLC:

Non-small cell lung cancer

hsa_circ_0020123:

Circ_0020123

qRT-PCR:

Quantitative real-time polymerase chain reaction

miR-1299:

MicroRNA-1299

RIP:

RNA immunoprecipitation

TSIIA:

Tanshinone IIA

PI:

Propidium iodide

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Acknowledgements

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Author notes

  1. Fei Sun and Xiaoli Yang contribute to this work equally as co-first authors.

Authors and Affiliations

  1. Department of Pharmacy, Yantai Hospital of Traditional Chinese Medicine, 39 Xingfu Road, Zhifu District, Yantai, 264000, Shandong, China

    Fei Sun & Qingyi Lin

  2. Department of Pharmacy, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China

    Xiaoli Yang

  3. Qingdao Central Hospital Drug Purchasing Office, Qingdao, Shandong, China

    Wei Song

  4. Department of Pharmacy, Qingdao Eighth People’s Hospital, Qingdao, Shandong, China

    Nan Yu

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  1. Fei Sun
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  4. Nan Yu
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  5. Qingyi Lin
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Contributions

Conceptualization and Methodology: XY and WS; Formal analysis and Data curation: CX, NY and QL; Validation and Investigation: FS and XY; Writing—original draft preparation and Writing—review and editing: FS, XY, WS and CX; Approval of final manuscript: all authors.

Corresponding author

Correspondence to Qingyi Lin.

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The present study was approved by the ethical review committee of Yantai Hospital of Traditional Chinese Medicine.

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Sun, F., Yang, X., Song, W. et al. Tanshinone IIA (TSIIA) represses the progression of non-small cell lung cancer by the circ_0020123/miR-1299/HMGB3 pathway. Mol Cell Biochem 478, 1973–1986 (2023). https://doi.org/10.1007/s11010-022-04646-3

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