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  • Title: Exosomal long non-coding RNA SOX2 overlapping transcript enhances the resistance to EGFR-TKIs in non-small cell lung cancer cell line H1975.
    Author: Zhou D, Xia Z, Xie M, Gao Y, Yu Q, He B.
    Journal: Hum Cell; 2021 Sep; 34(5):1478-1489. PubMed ID: 34244990.
    Abstract:
    Crosstalk between cancer cells and macrophages plays a crucial role in the development of cancer. In this study, our data showed that M1 macrophages attenuate, while M2 macrophages and tumor-associated macrophages enhance the EGFR-TKIs resistance in non-small cell lung cancer (NSCLC) cell line H1975. Next, long non-coding RNA SOX2 overlapping transcript (SOX2-OT) is highly expressed in NSCLC cells-derived exosomes. NSCLC cells-derived exosomes promote macrophages M2 polarization and inhibit M1 polarization through transferring SOX2-OT to macrophages. Subsequently, our results indicated that NSCLC cells-induced M2-polarized macrophages enhance the EGFR-TKIs resistance in H1975 cells. Furthermore, our data revealed that NSCLC cells-derived exosomes inhibit the expression of miR-627-3p, while promote Smads expression in THP-1 cells. SOX2-OT acts as miR-627-3p sponge to facilitate Smad2, Smad3 and Smad4 expression. Finally, our results indicated that NSCLC cells promote macrophages M2 polarization and suppress M1 polarization through targeting miR-627-3p/Smads signaling pathway by transferring exosomes to THP-1 cells. In conclusion, our data revealed that NSCLC cells promote macrophages M2 polarization through transferring exosomal SOX2-OT, thus to enhance its own EGFR-TKIs resistance. Mechanismly, NSCLC cells-derived exosomal SOX2-OT promotes macrophages M2 polarization via promoting Smads by sponging miR-627-3p. Our data provide a novel therapeutic target for EGFR-TKIs resistance in NSCLC.
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