长链非编码 RNA TUG1 通过调控 miR-320a/FOXQ1 轴促进膀胱癌恶性行为。
LncRNA TUG1 promotes bladder cancer malignant behaviors by regulating the miR-320a/FOXQ1 axis.
机构信息
Department of Urology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China.
Department of Andrology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, Guangdong Province, China.
出版信息
Cell Signal. 2022 Mar;91:110216. doi: 10.1016/j.cellsig.2021.110216. Epub 2021 Dec 14.
BACKGROUND
Growing evidence has showed long noncoding RNAs (lncRNAs) play critical roles in bladder cancer (BC) progression. LncRNA taurine upregulated gene 1 (TUG1) was involved in the development of human malignancies. However, the intrinsic and concrete molecular mechanisms of TUG1 in BC remain largely unknown.
METHODS
Expression patterns of TUG1, miR-320a and FOXQ1 in BC tissues and cell lines were measured using qRT-PCR and western blot, respectively. Cell proliferation was detected by CCK-8 and colony formation assays. The capacity of cell migration and invasion was evaluated using wound healing and transwell assay. Tumor xenograft assay was performed to further validate the role of TUG1 in BC progression. Dual luciferase reporter assay and FISH analysis were employed to verify the TUG1/miR-320a/FOXQ1 regulatory network.
RESULTS
TUG1 was significantly higher expression in BC specimens and cell lines. TUG1 knockdown suppressed BC cells malignant behaviors in vitro and inhibited tumor growth and metastasis in vivo, while TUG1 overexpression promoted BC cells malignant behaviors in vitro. However, the function of miR-320a was opposite to that of TUG1, and miR-320a inhibitor partially eliminated the inhibitory effect of TUG1 knockdown on the malignant behavior of BC cells. As a microRNA sponge, TUG1 actively elevated FOXQ1 expression to sponge miR-320a and subsequently promoted BC cells malignant phenotypes.
CONCLUSION
TUG1 may have great potential as therapeutic target for BC, since TUG1 silencing inhibited cell proliferation, migration and invasion in BC, while promoted cell apoptosis, by regulating the miR-320a/FOXQ1 axis.
背景
越来越多的证据表明，长链非编码 RNA（lncRNA）在膀胱癌（BC）进展中发挥着关键作用。lncRNA 牛磺酸上调基因 1（TUG1）参与了人类恶性肿瘤的发展。然而，TUG1 在 BC 中的内在和具体分子机制在很大程度上仍不清楚。
方法
使用 qRT-PCR 和 Western blot 分别检测 BC 组织和细胞系中 TUG1、miR-320a 和 FOXQ1 的表达模式。通过 CCK-8 和集落形成实验检测细胞增殖。使用划痕愈合和 Transwell 实验评估细胞迁移和侵袭能力。通过肿瘤异种移植实验进一步验证 TUG1 在 BC 进展中的作用。双荧光素酶报告基因实验和 FISH 分析用于验证 TUG1/miR-320a/FOXQ1 调控网络。
结果
TUG1 在 BC 标本和细胞系中表达明显升高。TUG1 敲低抑制 BC 细胞的恶性表型，体外抑制肿瘤生长和转移，体内过表达 TUG1 促进 BC 细胞的恶性表型。然而，miR-320a 的功能与 TUG1 相反，miR-320a 抑制剂部分消除了 TUG1 敲低对 BC 细胞恶性行为的抑制作用。作为一种 microRNA 海绵，TUG1 主动上调 FOXQ1 表达，以海绵 miR-320a，进而促进 BC 细胞的恶性表型。
结论
TUG1 可能作为 BC 的治疗靶点具有很大的潜力，因为 TUG1 沉默通过调节 miR-320a/FOXQ1 轴抑制了 BC 细胞的增殖、迁移和侵袭，同时促进了细胞凋亡。
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