Abstract
Background: Long non-coding RNAs have been reported to be involved in tumorigenesis and progression through different regulatory mechanisms. It has been reported that aberrantly expressed long non-coding RNA LINC00491 promotes malignancy in multiple tumors, while the role of LINC00491 in lung adenocarcinoma (LUAD) is little reported and the mechanism for regulating tumor progression has not been elucidated. Methods: RNA sequencing and the TCGA database were combined to screen differentially expressed lncRNAs that facilitate tumor progression. The expression level of LINC00491 was examined in LUAD clinical samples and in cell lines using RT-qPCR. In vitro experiments including colony formation assay, EdU assay, cell migration and invasion assay and wound healing assay, and in vivo experiments including xenografting subcutaneous tumors and lung metastasis models were performed to investigate the function of LINC00491 in LUAD tumor progressions. RNA pull-down, mass spectrometry, RIP assays and truncation experiments were carried out to explore the proteins binding to LINC00491 and the specific interactions between the RNA-protein complex. Results: Our results showed that LINC0491 was significantly upregulated in LUAD and positively correlated with poor survival. High LINC00491 expression promoted proliferation, migration and invasion, and resulted in a high metastatic burden in LUAD. Using pull-down assay and mass spectrometry, MTSS1 was found binding to LINC00491, and the conducted experiments verified the direct interaction between LINC00491 and MTSS1. Meanwhile, LINC00491 was found to regulate MTSS1 degradation by promoting the MTSS1 ubiquitination level and then activating the Wnt/β-catenin-signaling pathway. LINC00491/MTSS1/β-catenin may act as a complex to facilitate tumor progression. Conclusions: In summary, our results found a novel mechanism in which LINC00491 directly interacts with MTSS1 by affecting its ubiquitination modification to promote LUAD proliferation, migration and invasion, then activating the Wnt/β-catenin-signaling pathway, demonstrating its significant role in tumor progression and suggesting that the LINC00491/MTSS1/Wnt/β-catenin-signaling pathway could serve as a potential therapeutic target for lung adenocarcinoma in the future.