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

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
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长非编码RNA HIT000218960通过上调高迁移率组AT-hook 2 (HMGA2)基因的表达促进乳头状甲状腺癌肿瘤发生和肿瘤进展

DOI:
10.1080/15384101.2016.1261768
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发表时间:
2017-01-01
期刊:
影响因子:
4.3
通讯作者:
Wang, Shan
Wang, Shan
中科院分区:
生物学3区
文献类型:
--
作者:
Li, Tao;Yang, Xiao-dong;Wang, Shan

文献摘要

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越来越多的证据表明,长链非编码RNA(lncRNA)在肿瘤的发生和发展中起着重要作用。然而,我们对甲状腺癌中lncRNA的了解仍然有限。为探讨甲状腺乳头状癌(PTC)发生过程中的关键lncRNA,本研究通过lncRNA芯片获得PTC组织与癌旁正常甲状腺组织之间差异表达的lncRNA数据。在微阵列数据中,我们观察到一种新鉴定的lncRNA,HIT 000218960,在PTC组织中显著上调,并与一种众所周知的癌基因,高迁移率族AT-钩2(HMGA 2)基因相关。在正常甲状腺组织和甲状腺乳头状癌组织中,HIT 000218960和HMGA 2 mRNA的表达均呈显著正相关。在PTC细胞中敲低HIT 000218960导致HMGA 2下调。此外,功能测定表明,在PTC细胞中抑制HIT 000218960抑制细胞增殖、集落形成、迁移和体外侵袭。HIT 000218960在PTC组织中的高表达与淋巴结转移、多灶性及TNM分期有关。提示HIT 000218960可能通过调节HMGA 2的表达而发挥促癌作用。
ABSTRACT 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.