LncRNA RPPH1 promotes colorectal cancer metastasis by interacting with TUBB3 and by promoting exosomes-mediated macrophage M2 polarization

<jats:title>Abstract</jats:title><jats:p>Metastasis is a well-known poor prognostic factor in cancer. However, the mechanisms how long non-coding RNAs (lncRNAs) regulate metastasis in colorectal cancer (CRC) remain largely unknown. Besides, tumor-associated macrophages (TAMs) play an important role in tumor progression, yet the contribution of lncRNA-mediated crosstalk between TAMs and CRC cells to tumor progression is not well understood. In this study, we report that lncRNA <jats:italic>RPPH1</jats:italic> was significantly upregulated in CRC tissues, and the <jats:italic>RPPH1</jats:italic> overexpression was associated with advanced TNM stages and poor prognosis. <jats:italic>RPPH1</jats:italic> was found to promote CRC metastasis in vitro and in vivo. Mechanistically, <jats:italic>RPPH1</jats:italic> induced epithelial–mesenchymal transition (EMT) of CRC cells via interacting with β-III tubulin (TUBB3) to prevent its ubiquitination. Furthermore, CRC cell-derived exosomes transported <jats:italic>RPPH1</jats:italic> into macrophages which mediate macrophage M2 polarization, thereby in turn promoting metastasis and proliferation of CRC cells. In addition, exosomal <jats:italic>RPPH1</jats:italic> levels in blood plasma turned out to be higher in treatment-naive CRC patients but lower after tumor resection. Compared to CEA and CA199, exosomal <jats:italic>RPPH1</jats:italic> in CRC plasma displayed a better diagnostic value (AUC = 0.86). Collectively, <jats:italic>RPPH1</jats:italic> serves as a potential therapeutic and diagnostic target in CRC.</jats:p>