结直肠癌（CRC）是一种常见且致命的肿瘤，转移是死亡的主要原因。此前的研究表明，长链非编码RNA（lncRNA）CCAT2参与多种肿瘤进展机制的调节。然而，CCAT2 在 CRC 增殖和转移中的确切作用仍然不明确。本研究旨在阐明CCAT2影响CRC的机制。采用高通量测序和RT-qPCR检测CRC中CCAT2的表达。进行功能分析，包括 CCK8、集落形成、伤口愈合迁移、transwell 室和 Muse® 细胞分析仪测定，以研究 CCAT2 基因缺失对 CRC 细胞的影响。采用RNA下拉和蛋白质质谱法来鉴定CCAT2和GNB2蛋白之间的相互作用。在结直肠癌中发现CCAT2表达增加，尤其是在转移性结直肠癌中。 CCAT2基因的缺失抑制了CRC细胞的增殖、迁移和侵袭，同时促进了细胞凋亡。 CCAT2 和 GNB2 蛋白之间的相互作用被证明可以调节 GNB2 蛋白的改变并影响 ERK 和 Wnt 信号通路，从而促进 CRC 增殖和转移。CCAT2 通过与GNB2。这些发现强调了 CCAT2 作为 CRC 增殖和转移机制中关键调控元件的重要性。© 2024 作者。约翰·威利出版的癌症医学

Colorectal cancer (CRC) is a prevalent and lethal tumor, with metastasis being the leading cause of mortality. Previous research has indicated that the long non-coding RNA (lncRNA) CCAT2 is involved in the regulation of various tumor progression mechanisms. However, the precise role of CCAT2 in CRC proliferation and metastasis remains ambiguous. This study seeks to elucidate the mechanisms through which CCAT2 influences CRC.High-throughput sequencing and RT-qPCR were used to detect CCAT2 expression in CRC. Functional analyses including CCK8, colony formation, wound healing migration, transwell chamber, and Muse® Cell Analyzer assays were performed to study the effects of CCAT2 gene deletion on CRC cells. RNA-pulldown and protein mass spectrometry were employed to identify the interaction between CCAT2 and GNB2 protein.Increased CCAT2 expression was found in CRC, especially in metastatic CRC. Deletion of CCAT2 gene inhibited CRC cell proliferation, migration, and invasion while promoting apoptosis. The interaction between CCAT2 and GNB2 protein was shown to modulate GNB2 protein alterations and affect the ERK and Wnt signaling pathways, thereby promoting CRC proliferation and metastasis.CCAT2 plays a crucial role in CRC progression by modulating the ERK and Wnt signaling pathways through its interaction with GNB2. These findings highlight the importance of CCAT2 as a key regulatory element in the mechanisms underlying CRC proliferation and metastasis.© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.