长链非编码 RNA PVT1 通过与 miR-3619-5p 海绵吸附作用调节 TRIM29 表达促进结直肠癌的生长和转移。

BACKGROUND: Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide. Long noncoding RNA (lncRNA) is involved in many malignant tumors. This study aimed to clarify the role of the lncRNA plasmacytoma variant translocation 1 (PVT1) in CRC growth and metastasis. METHODS: Differentially expressed lncRNAs in CRC were analyzed using the Cancer Genome Atlas. Gene expression profiling interactive analysis and a comprehensive resource for lncRNAs from cancer arrays databases were used to analyze lncRNA PVT1 expression and CRC prognosis, respectively. Cell counting kit-8, wound healing, colony formation, Transwell, and immunofluorescence assays were used to evaluate CRC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), respectively. Tumor growth and metastasis models were used to explore the PVT1 effect on the growth and metastasis of CRC in vivo. RESULTS: PVT1 was highly expressed in CRC, associated with a poor prognosis of CRC, and showed good diagnostic value. Transfection of sh-PVT1 or pcDNA3.1-PVT1 reduced or increased the proliferation, wound healing rate, colony formation, invasion, and EMT of CRC cells. PVT1 and miR-3619-5p were co-expressed in CRC cytoplasm, and PVT1 acted as a competitive endogenous RNA (ceRNA) by sponging miR-3619-5p to up-regulate tripartite motif containing 29 (TRIM29) expression. MiR-3619-5p overexpression and TRIM29 knockdown reduced proliferation, wound healing rate, invasion, and EMT of CRC cells. However, simultaneous PVT1 and miR-3619-5p overexpression or knockdown of miR-3619-5p and TRIM29 knockdown rescued the malignant phenotype of CRC cells. CONCLUSIONS: We first clarified the ceRNA mechanism of PVT1 in CRC, which induced growth and metastasis by sponging with miR-3619-5p to regulate TRIM29.

背景：结直肠癌（CRC）是全球癌症相关死亡的第二大主要原因。长链非编码 RNA（lncRNA）参与许多恶性肿瘤。本研究旨在阐明浆细胞瘤变异易位 1（PVT1）lncRNA 在 CRC 生长和转移中的作用。

方法：使用癌症基因组图谱分析 CRC 中差异表达的 lncRNA。基因表达谱交互分析和癌症阵列数据库的综合 lncRNA 资源分别用于分析 lncRNA PVT1 表达和 CRC 预后。细胞计数试剂盒-8、划痕愈合、集落形成、Transwell 和免疫荧光测定分别用于评估 CRC 细胞的增殖、迁移、侵袭和上皮-间充质转化（EMT）。肿瘤生长和转移模型用于探索 PVT1 对 CRC 体内生长和转移的影响。

结果：PVT1 在 CRC 中高表达，与 CRC 预后不良相关，具有良好的诊断价值。sh-PVT1 或 pcDNA3.1-PVT1 的转染降低或增加了 CRC 细胞的增殖、划痕愈合率、集落形成、侵袭和 EMT。PVT1 和 miR-3619-5p 在 CRC 细胞质中共表达，PVT1 通过海绵 miR-3619-5p 作为竞争性内源性 RNA（ceRNA）上调三部分结构域 29（TRIM29）的表达。miR-3619-5p 过表达和 TRIM29 敲低降低了 CRC 细胞的增殖、划痕愈合率、侵袭和 EMT。然而，同时过表达 PVT1 和 miR-3619-5p 或敲低 miR-3619-5p 和 TRIM29 敲低挽救了 CRC 细胞的恶性表型。

结论：我们首次阐明了 PVT1 在 CRC 中的 ceRNA 机制，该机制通过与 miR-3619-5p 结合并调节 TRIM29 来诱导生长和转移。