MicroRNA-1280 inhibits invasion and metastasis by targeting ROCK1 in bladder cancer.
MicroRNA-1280 inhibits invasion and metastasis by targeting ROCK1 in bladder cancer.
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DOI：
10.1371/journal.pone.0046743
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Dahiya R
中科院分区：
文献类型：
--
作者：
Majid S;Dar AA;Saini S;Shahryari V;Arora S;Zaman MS;Chang I;Yamamura S;Chiyomaru T;Fukuhara S;Tanaka Y;Deng G;Tabatabai ZL;Dahiya R
微小RNA（microRNAs，miRNAs）是一类非蛋白质编码序列，可作为癌基因或抑癌基因发挥功能。这项研究记录了miR-1280在膀胱癌中的肿瘤抑制作用。定量实时PCR和原位杂交分析显示，与非恶性细胞系或正常组织样品相比，miR-1280在膀胱癌细胞系和肿瘤中显著下调。为了解读miR-1280在膀胱癌中的功能意义，我们在膀胱癌细胞系中异位过表达miR-1280。过表达miR-1280对膀胱癌细胞系具有抗增殖作用，并损害其集落形成。流式细胞仪（fluorescence activated cell sorting，FACS）分析显示，miR-1280在膀胱癌细胞中的重新表达可诱导G2-M期细胞阻滞和凋亡。我们的结果表明，miR-1280抑制膀胱癌细胞系的迁移和侵袭。miR-1280还减弱ROCK 1和RhoC蛋白表达。荧光素酶报告基因分析表明，癌基因ROCK 1是膀胱癌中miR-1280的直接靶点。这项研究还表明，miR-1280可能在膀胱癌的诊断和预后中具有重要意义。例如，ROC分析显示miR-1280表达可以区分恶性和正常膀胱癌病例，Kaplan-Meier分析显示miR-1280高表达患者的总生存率高于miR-1280低表达患者。总之，这是第一项研究证明miR-1280通过靶向癌基因ROCK 1来发挥肿瘤抑制剂的作用，以促进侵袭/迁移和转移。各种化合物目前被用作ROCK 1抑制剂;因此，肿瘤抑制剂miR-1280的恢复可能在膀胱癌的治疗中单独或与这些化合物组合在治疗上有用。
MicroRNAs (miRNAs) are non-protein-coding sequences that can function as oncogenes or tumor suppressor genes. This study documents the tumor suppressor role of miR-1280 in bladder cancer. Quantitative real-time PCR and in situ hybridization analyses showed that miR-1280 is significantly down-regulated in bladder cancer cell lines and tumors compared to a non-malignant cell line or normal tissue samples. To decipher the functional significance of miR-1280 in bladder cancer, we ectopically over-expressed miR-1280 in bladder cancer cell lines. Over-expression of miR-1280 had antiproliferative effects and impaired colony formation of bladder cancer cell lines. FACS (fluorescence activated cell sorting) analysis revealed that re-expression of miR-1280 in bladder cancer cells induced G2-M cell cycle arrest and apoptosis. Our results demonstrate that miR-1280 inhibited migration and invasion of bladder cancer cell lines. miR-1280 also attenuated ROCK1 and RhoC protein expression. Luciferase reporter assays demonstrated that oncogene ROCK1 is a direct target of miR-1280 in bladder cancer. This study also indicates that miR-1280 may be of diagnostic and prognostic importance in bladder cancer. For instance, ROC analysis showed that miR-1280 expression can distinguish between malignant and normal bladder cancer cases and Kaplan-Meier analysis revealed that patients with miR-1280 high expression had higher overall survival compared to those with low miR-1280 expression. In conclusion, this is the first study to document that miR-1280 functions as a tumor suppressor by targeting oncogene ROCK1 to invasion/migration and metastasis. Various compounds are currently being used as ROCK1 inhibitors; therefore restoration of tumor suppressor miR-1280 might be therapeutically useful either alone or in combination with these compounds in the treatment of bladder cancer.
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