Department of Oncology, Qingdao Municipal Hospital, Medical College of Qingdao University Qingdao, Qingdao, Shandong, People's Republic of China.
Department of Oncology, Qingdao women and children's Hospital, Qingdao, Shandong, People's Republic of China.
Cancer Rep (Hoboken). 2024 Jun;7(6):e2085. doi: 10.1002/cnr2.2085.
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.
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.
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.
We first clarified the ceRNA mechanism of PVT1 in CRC, which induced growth and metastasis by sponging with miR-3619-5p to regulate TRIM29.
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。
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。
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。
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。
