circLPAR1 is a novel biomarker of prognosis for muscle-invasive bladder cancer with invasion and metastasis by miR-762
circLPAR1 is a novel biomarker of prognosis for muscle-invasive bladder cancer with invasion and metastasis by miR-762
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circLPAR1是miR-762侵袭和转移的肌层浸润性膀胱癌预后的新型生物标志物
DOI：
10.3892/ol.2019.9970
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发表时间：
2019-03-01
期刊：
影响因子：
2.9
通讯作者：
Ye, Dingwei
中科院分区：
文献类型：
--
作者：
Lin, Guowen;Sheng, Haoyue;Ye, Dingwei
环状RNAs(CircRNAs)是一种特定形式的非编码RNAs，在包括阿尔茨海默病和癌症在内的人类疾病的发展中起着关键作用；然而，只有少数人知道与癌症有关的信息。本研究在肌肉浸润性膀胱癌组织中发现了一种新的环状RNA，CIRC溶血磷脂酸受体1(HSA_CIRC_0087960)，它来源于两个外显子226个碱基对。通过单因素和多因素COX回归分析，发现CircLPAR1在MIBC125例组织中低表达，与高表达的患者(52.4vs.56.0月；P=0.001)相比，其疾病特异性生存时间较短。Matrigel和伤口愈合实验也显示，小干扰RNAi-CircLPAR1-1在T24细胞株中的表达显著增强了膀胱癌细胞的侵袭力(在T24细胞中的si-CircLPAR1-1，P=0.003；在T24细胞中的si-CircLPAR1-2，P=0.002；在5637细胞中的si-CircLPAR1-2，P=0.006)。生物信息学分析表明，根据miRNAs种子序列匹配，CircLPAR1可能含有特定的microRNAs(MiRNAs)。荧光素酶报告基因检测表明，miR-762插入到CircLPAR1野生型片段中可以抑制荧光素酶基因的活性，而当荧光素酶基因插入带有突变的miR-762靶点的CircLPAR1片段中时，这种抑制作用可以被缓解。综上所述，CircLPAR1可能是一种新的、稳定的MIBC预后标志物，并可能与miR-762的侵袭转移有关。
Circular RNAs (circRNAs) are a specific form of non-coding RNAs, that serve a pivotal role in the development of human diseases, including Alzheimer's disease and cancer; however, only a few are known with respect to cancer. The present study identified a novel circRNA, circ lysophosphatidic acid receptor 1 (LPAR1) (hsa_circ_0087960), derived from two exons 226 base pairs in length, in muscle-invasive bladder cancer (MIBC) tissues. circLPAR1 was identified to be lowly expressed in MIBC tissues in a cohort of 125 cases, and predicted a poor disease-specific survival time, compared with patients with high circLPAR1 expression (52.4 vs. 56.0 months; P=0.001) by univariate and multivariate Cox regression analyses. Matrigel and wound healing assays also demonstrated that the invasion of 5637 and T24 bladder cancer cells were significantly enhanced following the knockdown of circLPAR1 by small interfering RNA (si-circLPAR1-1 in T24 cell line, P=0.01; si-circLPAR1-2 in 5637 cell line, P=0.003; si-circLPAR1-2 in T24 cell line, P=0.002; si-circLPAR1-2 in 5637 cell line, P=0.006). The bioinformatics analysis indicated that circLPAR1 may harbor specific microRNAs (miRNAs) according to the miRNAs seed sequence matching. A luciferase reporter assay revealed that miR-762 can inhibit the activity of the transfected luciferase gene when inserted in a circLPAR1 wild-type fragment, and this inhibition could be alleviated when the luciferase gene was inserted in a circLPAR1 fragment with the mutated miR-762 target site. In conclusion, the circLPAR1 may function as a potential novel and stable biomarker for the prognosis of MIBC and may be associated with the invasion and metastasis by miR-762.