Long noncoding RNA UCA1 promotes anaplastic thyroid cancer cell proliferation via iniR-135a-mediated c-myc activation
Long noncoding RNA UCA1 promotes anaplastic thyroid cancer cell proliferation via iniR-135a-mediated c-myc activation
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DOI：
10.3892/mmr.2018.9276
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发表时间：
2018-09-01
影响因子：
3.4
通讯作者：
Li, Dong
中科院分区：
文献类型：
--
作者：
Wang, Yonghui;Hou, Zhengguang;Li, Dong
长链非编码RNA（lncRNA），尿路上皮癌相关1（UCA 1），已被证明是失调，并在几种癌症类型的进展中发挥作用。然而，UCA 1在甲状腺未分化癌（ATC）中的确切作用和潜在分子机制仍不清楚。本研究的目的是探讨UCA 1在ATC细胞增殖过程中的作用及其机制。本研究发现，UCA 1在ATC细胞系和组织中的表达水平分别与正常人甲状腺细胞系和邻近非癌组织相比显著上调。UCA 1基因敲低可显著抑制ATC细胞的存活、增殖、迁移和侵袭能力，抑制ATC细胞c-myc原癌基因（c-myc）的表达，抑制ATC肿瘤的生长。此外，使用荧光素酶测定，证实了miR-135 a直接结合UCA 1和c-myc的3'非翻译区，并且UCA 1与c-myc竞争miR-135 a结合。miR-135 a抑制可上调c-myc表达，然而，c-myc的上调可被短发夹UCA 1部分降低。本研究结果表明，UCA 1通过与miR-135 a结合，作为竞争性内源性RNA，促进ATC细胞增殖。总之，在本研究中，UCA 1作为一种致癌的长非编码RNA促进ATC细胞增殖，并可能成为人类ATC治疗的潜在靶点。
The long non-coding RNA (lncRNA), urothelial carcinoma-associated 1 (UCA1), has been demonstrated to be dysregulated and serves a role in the progression of several cancer types. However, the exact effects and underlying molecular mechanisms of UCA1 in anaplastic thyroid cancer (ATC) remain unknown. The aim of the present study was to investigate the detailed function and the mechanism of UCA1 in the regulation of ATC cell progression. The present study identified that the expression levels of UCA1, in ATC cell lines and tissues, were significantly upregulated compared with normal human thyroid cell line and adjacent non-cancerous tissues, respectively. UCA1 knockdown significantly inhibited ATC cell viability, proliferation, migration and invasion and the expression level of c-myc proto-oncogene (c-myc) in vitro, and suppressed ATC tumor growth in vivo. In addition, using luciferase assays, it was confirmed that miR-135a directly bound to UCA1 and the 3' untranslated region of c-myc, and UCA1 competed with c-myc for miR-135a binding. miR-135a inhibition may upregulate c-myc expression, however, the upregulation of c-myc may be partially reduced by short hairpin UCA1. The present results illustrated that UCA1 promoted ATC cell proliferation through acting as a competing endogenous RNA by binding miR-135a. In conclusion, in the present study, UCA1 served as an oncogenic long non-coding RNA promoting ATC cell proliferation and may be a potential target for human ATC treatment.