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Exosomal circ_PIP5K1A regulates the progression of non-small cell lung cancer and cisplatin sensitivity by miR-101/ABCC1 axis

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Abstract

Circular RNAs (circRNAs) play vital roles in various types of cancer and chemosentivity. In the progression of carcinogenesis, exosomes are messengers for intercellular communication. The aim of this study was to explore the role of exosomal circRNA phosphatidylinositol-4-phosphate 5-kinase type 1 alpha (circ_PIP5K1A) in non-small cell lung cancer (NSCLC) progression and cisplatin sensitivity. The expression levels of circ_PIP5K1A, miR-101 and ATP binding cassette subfamily C member 1 (ABCC1) were detected by quantitative real-time polymerase chain reaction or western blot assay. Cell Counting Kit-8 assay was used to detect cell viability and 50% inhibitory concentration value of cisplatin. Cell migration, invasion, proliferation, and apoptosis were determined by wound healing assay, transwell assay, colony formation assay, and flow cytometry, respectively. A xenograft tumor model was established to explore the role of circ_PIP5K1A in vivo. Exosomes were detected using transmission electron microscopy analysis. The interaction between miR-101 and circ_PIP5K1A or ABCC1 was predicted by bioinformatics analysis and verified by dual-luciferase reporter assay and RNA pull-down assay. Circ_PIP5K1A and ABCC1 were overexpressed and miR-101 was downregulated in NSCLC tissues, serum samples, and cells. Knockdown of exosomal circ_PIP5K1A inhibited NSCLC cell proliferation, migration, and invasion and promoted apoptosis and cisplatin sensitivity. Likewise, circ_PIP5K1A downregulation inhibited tumor growth. MiR-101 was a direct target of circ_PIP5K1A, and its knockdown reversed the effects of circ_PIP5K1A silence on inhibition of NSCLC progression and promotion of cisplatin sensitivity. Moreover, ABCC1 was a downstream target of miR-101, and miR-101 overexpression inhibited the progression of NSCLC cells and increased cisplatin sensitivity by targeting ABCC1. Besides, circ_PIP5K1A positively regulated ABCC1 expression by sponging miR-101. Exosomal circ_PIP5K1A knockdown inhibited NSCLC progression and promoted cisplatin sensitivity by regulating miR-101/ABCC1 axis, providing a novel avenue for treatment of NSCLC.

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Acknowledgements

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Funding

This work was supported by Medical and Health Science and Technology Development Plan of Shandong province (NO:2016WS0415).

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Authors and Affiliations

  1. Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jingwuweiqi Road, Huaiyin District, Jinan, 250021, Shandong, China

    Na Shao & Xiaogang Sun

  2. Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China

    Liang Song

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Correspondence to Xiaogang Sun.

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Shao, N., Song, L. & Sun, X. Exosomal circ_PIP5K1A regulates the progression of non-small cell lung cancer and cisplatin sensitivity by miR-101/ABCC1 axis. Mol Cell Biochem 476, 2253–2267 (2021). https://doi.org/10.1007/s11010-021-04083-8

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