Zhou Jun, Wang Chenghai, Huang Caihong, Ding Zhiyan, Shi Minhua
Department of Respiratory Medicine, The 2nd Affiliated Hospital of Soochow University 1055 Sanxiang Road, Suzhou 215004, Jiangsu, China.
Department of Respiratory Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou University Yangzhou, China.
Int J Clin Exp Pathol. 2018 Mar 1;11(3):1289-1296. eCollection 2018.
Transcribed ultraconserved regions (TUCRs) belong to long non-coding RNAs (lncRNAs) are transcripts longer than 200 base pair RNA with no protein-coding capacity. Previous studies showed that TUCRs serve as oncogenes or tumor suppressor genes are involved in tumorigenesis and cancer progressive. However, little is known about the expression level and biological role of TUCR.454 in lung carcinoma. Our data showed TUCR.454 is significantly down-regulated in NSCLC tissue and lung cancer cell lines, and the down-regulated TUCR.454 is associated with lymph node metastasis. Transfection with TUCR.454 markedly inhibited cell migration and invasion in A549 and H460 lung cancer cell lines. K-Ras was demonstrated to be negatively regulated by TUCR.454 at the posttranscriptional level by dual-luciferase reporter assay. Down-expression of K-Ras via siRNA inhibited NSCLC cell migration and down-regulates P63 and MMP9 in protein level, resembling that of overexpression of TUCR.454. In conclusion, these findings suggested that TUCR.454 acts as a novel tumor suppressor by targeting the K-Ras gene thus inhabiting lung cancer cell migration and invasion.
转录超保守区域(TUCRs)属于长链非编码RNA(lncRNAs),是长度超过200个碱基对且无蛋白质编码能力的转录本。先前的研究表明,TUCRs作为癌基因或肿瘤抑制基因参与肿瘤发生和癌症进展。然而,关于TUCR.454在肺癌中的表达水平和生物学作用知之甚少。我们的数据显示,TUCR.454在非小细胞肺癌组织和肺癌细胞系中显著下调,且下调的TUCR.454与淋巴结转移相关。用TUCR.454转染可显著抑制A549和H460肺癌细胞系中的细胞迁移和侵袭。双荧光素酶报告基因检测表明,K-Ras在转录后水平受到TUCR.454的负调控。通过小干扰RNA(siRNA)下调K-Ras可抑制非小细胞肺癌细胞迁移,并在蛋白质水平下调P63和MMP9,类似于TUCR.454过表达的情况。总之,这些发现表明,TUCR.454通过靶向K-Ras基因发挥新型肿瘤抑制作用,从而抑制肺癌细胞的迁移和侵袭。