Department of Urology, Hospital (T·C·M) Affiliated to Southwest Medical University, Sichuan, China.
Department of Pharmacology, School of Pharmacy, Southwest Medical University, Sichuan, China.
J Gene Med. 2020 Sep;22(9):e3210. doi: 10.1002/jgm.3210. Epub 2020 May 29.
Muscle-invasive bladder cancer (MIBC), a bladder cancer that spreads into the detrusor muscle of the bladder, leads to a poor outcome. Long noncoding RNA LINC00675 has been reported to play import roles in several cancer types, although its biological function and underlying mechanism in MIBC remain largely unclear.
Eighty-nine patients with MIBC were enrolled in the present study. RNA expression was measured using a quantitative reverse transcription-polymerase chain reaction. Protein expression was detected using western blotting. Transwell assays were performed to analyze the abilities of bladder cancer cells to migrate and invade. An RNA microarray was carried out to analyze LINC00675-regulated mRNAs in bladder cancer cells.
We found that LINC00675 expression was decreased in MIBC tissues compared to matched normal tissues, and was correlated with lymph node-metastatic MIBC. MIBC patients with low expression of LINC00675 had worse survival rates than those with high expression. Functional investigation showed that ectopic expression of LINC00675 inhibited bladder cancer cell migration, invasion and proliferation, whereas LINC00675 knockdown presented an opposite effect. Mechanistically, we found that LINC00675 inhibited β-catenin and its downstream gene expression.
The findings of the present study suggest that LINC00675 regulates β-catenin expression, and is associated with bladder cancer metastasis and patient survival.
肌层浸润性膀胱癌(MIBC)是一种扩散到膀胱逼尿肌的膀胱癌,导致预后不良。长链非编码 RNA LINC00675 已被报道在几种癌症类型中发挥重要作用,尽管其在 MIBC 中的生物学功能和潜在机制仍很大程度上不清楚。
本研究纳入了 89 例 MIBC 患者。使用定量逆转录聚合酶链反应测量 RNA 表达。使用 Western blot 检测蛋白表达。进行 Transwell 测定以分析膀胱癌细胞的迁移和侵袭能力。进行 RNA 微阵列分析以分析膀胱癌细胞中 LINC00675 调节的 mRNAs。
我们发现 LINC00675 在 MIBC 组织中的表达低于匹配的正常组织,并且与淋巴结转移性 MIBC 相关。LINC00675 低表达的 MIBC 患者的生存率低于高表达的患者。功能研究表明,LINC00675 的异位表达抑制了膀胱癌细胞的迁移、侵袭和增殖,而 LINC00675 的敲低则呈现相反的效果。机制上,我们发现 LINC00675 抑制了β-连环蛋白及其下游基因的表达。
本研究的结果表明,LINC00675 调节β-连环蛋白的表达,与膀胱癌转移和患者生存有关。