Wang C, Yan G, Zhang Y, Jia X, Bu P
Neoplasma. 2015;62(4):541-9. doi: 10.4149/neo_2015_065.
Thyroid cancer, the most common primary endocrine malignancy in adult, imperatively requires new therapeutic studies that could target the molecular regulatory mechanism. Even though emerging evidence showed that long noncoding RNAs (Lnc-RNAs) are involved in different biological characteristic of malignant tumor, such as cell growth and apoptosis as well as cancer progression and metastasis. Limited data are available on the function of Lnc-RNAs in thyroid cancer invasion and metastasis. Among the 5 tested lnc-RNAs , the present study demonstrates that MEG3 was significantly down-regulated in papillary thyroid carcinoma (PTC) tissues with lymph-node metastasis than in primary thyroid cancer. Moreover, the down- regulated MEG3 was associated with lymph-node metastasis. Over-expression of MEG3 could strongly inhibit the cell migration and invasion in TPC-1 and HTH83 thyroid cancer cell lines. In addition, we also showed that Rac1 was negatively regulated by lncRNA-MEG3 at the posttranscriptional level, via a specific target site within the 3΄UTR by dual luciferase reporter assay. The expression of Rac1 was inversely correlated with lncRNA-MEG3 expression in PTC tissues. Thus, this study suggests that MEG3 acts as novel suppressor of migration and invasion by targeting Rac1 gene.
甲状腺癌是成人中最常见的原发性内分泌恶性肿瘤,迫切需要针对分子调控机制的新治疗研究。尽管新出现的证据表明长链非编码RNA(Lnc-RNAs)参与了恶性肿瘤的不同生物学特性,如细胞生长、凋亡以及癌症进展和转移。关于Lnc-RNAs在甲状腺癌侵袭和转移中的功能,现有数据有限。在5种检测的lnc-RNAs中,本研究表明,与原发性甲状腺癌相比,伴有淋巴结转移的甲状腺乳头状癌(PTC)组织中MEG3显著下调。此外,MEG3下调与淋巴结转移有关。MEG3的过表达可强烈抑制TPC-1和HTH83甲状腺癌细胞系的细胞迁移和侵袭。此外,我们还通过双荧光素酶报告基因检测表明,lncRNA-MEG3在转录后水平通过3΄UTR内的一个特定靶位点对Rac1进行负调控。在PTC组织中,Rac1的表达与lncRNA-MEG3的表达呈负相关。因此,本研究表明MEG3通过靶向Rac1基因,作为迁移和侵袭的新型抑制因子。