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Serum LUCAT1 implicates the pathogenesis of muscle-invasive bladder cancer via targeting miR-199a-5p and miR-199b-5p.
Journal of Molecular Histology ( IF 2.9 ) Pub Date : 2020-08-25 , DOI: 10.1007/s10735-020-09907-3
Yong Zhou 1 , Xuejing Song 1 , Xiameng Li 1 , Huimin Li 1 , Ying Peng 1, 2
Affiliation  

Muscle-invasive bladder cancer (MIBC) is a common malignancy of urinary system cancers, accounting for about 1/3 of all newly diagnosed bladder cancer cases. Due to its strong metastasis, the 5-year survival of MIBC is less than 50%, and in serious cases, the overall survival of metastatic bladder cancer patients is about 1.3 years. LncRNAs, a type of non-coding RNAs defined as the transcripts exceeding 200 nucleotides in length, are frequently aberrant in multiple cancers including cervical, ovarian, breast and bladder cancers. Recently, LUCAT1 (short for lung cancer-associated transcript 1), a lncRNA first reported to be involved in smoking-related lung cancer, has been observed to exhibit crucial roles in the epithelial-to-mesenchymal transition (EMT), migration and invasion processes of clear cell renal cell carcinoma (ccRCC) and colorectal cancer. However, whether it involves in the pathogenesis of MIBC remains underexplored. In the present study, LUCAT1 was up-regulated in the serum samples of MIBC patients and bladder cancer cell lines, as assessed using real-time PCR. Our in vitro data (including wound healing and trans-well assays) showed that LUCAT1 was required for the proliferation, EMT, migration and invasion processes of T24 cells. Moreover, LUCAT1 directly targeted miR-199a-5p and miR-199b-5p, as affirmed using the luciferase reporter assay, and manipulation of LUCAT1 significantly suppressed miR-199a-5p and miR-199b-5p. Collectively, our findings highlight an axis of LUCAT1/miR-199a/b-5p in MIBC pathogenesis. Therefore, LUCAT1 may possibly be a promising candidate for diagnostic biomarker and therapeutic target of MIBC.



中文翻译:

血清LUCAT1通过靶向miR-199a-5p和miR-199b-5p牵涉肌肉浸润性膀胱癌的发病机理。

肌肉浸润性膀胱癌(MIBC)是泌尿系统癌症的常见恶性肿瘤,约占所有新诊断的膀胱癌病例的1/3。由于其强大的转移能力,MIBC的5年生存率不到50%,在严重的情况下,转移性膀胱癌患者的总体生存期约为1.3年。LncRNA是一种非编码RNA,定义为长度超过200个核苷酸的转录本,经常在多种癌症中异常出现,包括宫颈癌,卵巢癌,乳腺癌和膀胱癌。最近,有人发现LUCAT1(肺癌相关转录本1的缩写)是一种最早报道与吸烟有关的肺癌的lncRNA,在上皮-间质转化(EMT)中发挥着关键作用,透明细胞肾细胞癌(ccRCC)和结直肠癌的迁移和侵袭过程。但是,它是否参与MIBC的发病机理仍待探讨。在本研究中,通过实时PCR评估,在MIBC患者和膀胱癌细胞系的血清样品中LUCAT1上调。我们的体外数据(包括伤口愈合和跨孔测定)表明,LUCAT1是T24细胞增殖,EMT,迁移和侵袭过程所必需的。此外,LUCAT1直接靶向miR-199a-5p和miR-199b-5p(使用萤光素酶报告基因测定法证实),操纵LUCAT1可以显着抑制miR-199a-5p和miR-199b-5p。总的来说,我们的发现突出了MICAT发病机制中LUCAT1 / miR-199a / b-5p的轴。因此,

更新日期:2020-08-26
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