Long noncoding RNA HIT000218960 promotes papillary thyroid cancer oncogenesis and tumor progression by upregulating the expression of high mobility group AT-hook 2 (HMGA2) gene

Accumulating evidence suggests that long noncoding RNAs (lncRNAs) play an important role in oncogenesis and tumor progression. However, our knowledge of lncRNAs in thyroid cancer is still limited. To explore the crucial lncRNAs involved in oncogenesis of papillary thyroid cancer (PTC), we acquired data of differentially expressed lncRNAs between PTC tissues and paired adjacent noncancerous thyroid tissues through lncRNA microarray. In the microarray data, we observed that a newly identified lncRNA, HIT000218960, was significantly upregulated in PTC tissues and associated with a well-known oncogene, high mobility group AT-hook 2 (HMGA2) gene. Both in normal thyroid tissues and PTC tissues, the expression of HIT000218960 was significantly positively correlated with that of HMGA2 mRNA. Knockdown of HIT000218960 in PTC cells resulted in downregulation of HMGA2. In addition, functional assays indicated that inhibition of HIT000218960 in PTC cells suppressed cell proliferation, colony formation, migration and invasion in vitro. Increased HIT000218960 expression in PTC tissues was obviously correlated with lymph node metastasis and multifocality, as well as TNM stage. Those findings suggest that HIT000218960 might acts as a tumor promoter through regulating the expression of HMGA2.

越来越多的研究证据表明，长链非编码RNA（long noncoding RNAs）在肿瘤发生与肿瘤进展中发挥重要作用。然而，目前学界对甲状腺癌中lncRNAs的认知仍较为有限。为了探究参与甲状腺乳头状癌（papillary thyroid cancer，PTC）发生的关键lncRNAs，我们通过lncRNA微阵列获取了PTC组织与其配对的癌旁正常甲状腺组织之间的差异表达lncRNAs数据。在该微阵列数据中，我们观察到一条新鉴定出的lncRNA——HIT000218960在PTC组织中显著上调，且与已知癌基因高迁移率族AT钩蛋白2（high mobility group AT-hook 2，HMGA2）存在关联。无论是正常甲状腺组织还是PTC组织，HIT000218960的表达水平均与HMGA2 mRNA的表达水平呈显著正相关。在PTC细胞中敲低HIT000218960会导致HMGA2的表达下调。此外，功能实验结果显示，抑制PTC细胞中HIT000218960的表达可在体外抑制细胞增殖、集落形成、迁移与侵袭能力。PTC组织中HIT000218960的高表达与淋巴结转移、多灶性及TNM分期均显著相关。上述研究结果表明，HIT000218960可能通过调控HMGA2的表达发挥促肿瘤作用。