Department of Urology, The First People's Hospital of Wenling, Wenling, Zhejiang 317500, P.R. China.
Oncol Rep. 2021 Apr;45(4). doi: 10.3892/or.2021.7959. Epub 2021 Mar 2.
The aim of the present study was to explore the effects of LINC00649 on the proliferation, migration and invasion of bladder cancer (BC) and identify possible mechanisms. Through TCGA database analysis of LINC00649 expression in bladder cancer and the association of LINC00649 with the BC patient prognosis, RT‑qPCR was employed for detecting LINC00649 expression in 60 clinical tissue specimens and cell lines of bladder cancer. The lentivirus stable transfection or small interfering RNA was used to increase or decrease the LINC00649 expression level in T24 and UM‑UC‑3 cells. CCK8 and clone formation assay were utilized to observe the effects of LINC00649 on the proliferation and colony formation of BC cells. Transwell experiment was performed to detect the effects of LINC00649 on the migration and invasion of bladder cancer. Bioinformatics database was used to identify the possible downstream targets of LINC00649 while RT‑qPCR, western blot analysis and dual luciferase reporter gene experiments were carried out to verify the possible molecular mechanism. The TCGA database analysis revealed a significantly high expression of LINC00649 in bladder cancer and an association of LINC00649 expression with overall survival rate of BC patients. As shown by RT‑qPCR detection, LINC00649 expression was notably upregulated in BC tissues and BC cell lines. In addition, statistical analyses unveiled that highly expressed LINC00649 was clearly associated with poor overall survival of bladder cancer. Based on the cell experiment, upregulated LINC00649 considerately enhanced the proliferation, migration and invasion of BC cells, as opposed to those in T24 and UM‑UC‑3 cells by suppressing LINC00649. Mechanically, LINC00649 may promote the malignant progression of bladder cancer by regulating miR‑15a‑5p to promote the HMGA1 expression axis. Overall, LINC00649 upregulates HMGA1 expression by binding to miR‑15a‑5p to enhance the proliferation, migration and invasion of BC cells. Thus, LINC00649 is a potential biomarker and therapeutic target for bladder cancer.
本研究旨在探讨 LINC00649 对膀胱癌（BC）增殖、迁移和侵袭的影响，并确定可能的机制。通过 TCGA 数据库分析 LINC00649 在膀胱癌中的表达及其与 BC 患者预后的关系，采用 RT-qPCR 检测 60 例临床组织标本和膀胱癌细胞系中 LINC00649 的表达。采用慢病毒稳定转染或小干扰 RNA 增加或减少 T24 和 UM-UC-3 细胞中 LINC00649 的表达水平。CCK8 和克隆形成实验用于观察 LINC00649 对 BC 细胞增殖和集落形成的影响。Transwell 实验用于检测 LINC00649 对膀胱癌迁移和侵袭的影响。生物信息学数据库用于鉴定 LINC00649 的可能下游靶标，同时进行 RT-qPCR、Western blot 分析和双荧光素酶报告基因实验以验证可能的分子机制。TCGA 数据库分析显示，LINC00649 在膀胱癌中表达明显升高，LINC00649 表达与 BC 患者总生存率相关。RT-qPCR 检测结果显示，LINC00649 在 BC 组织和 BC 细胞系中表达明显上调。此外，统计分析表明，高表达的 LINC00649 与膀胱癌患者的总生存期明显相关。基于细胞实验，上调 LINC00649 可通过抑制 LINC00649 显著促进 BC 细胞的增殖、迁移和侵袭，而下调 LINC00649 则可显著抑制 BC 细胞的增殖、迁移和侵袭。在机制上，LINC00649 通过调节 miR-15a-5p 促进 HMGA1 表达轴，从而促进膀胱癌的恶性进展。总之，LINC00649 通过与 miR-15a-5p 结合上调 HMGA1 表达，增强 BC 细胞的增殖、迁移和侵袭。因此，LINC00649 是膀胱癌潜在的生物标志物和治疗靶点。
