Department of Head and Neck Surgery, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union.
Eur Rev Med Pharmacol Sci. 2019 Feb;23(3):1134-1144. doi: 10.26355/eurrev_201902_17004.
Long noncoding RNA LINC00313 (LINC00313) has been reported to be dysregulated in several tumors, including papillary thyroid carcinoma (PTC). Our present study aimed to further explore the potential mechanism of LINC00313 in the progression of papillary thyroid carcinoma (PTC).
RT-PCR was performed to detect the expression of LINC00313 in both PTC tissues and cell lines. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were performed to explore whether SP1 could bind to the promoter region of LINC00313 and activate its transcription. The biological functional correlation of LINC00313 was determined by down-regulating the expression of LINC00313 on PTC cell proliferation, apoptosis, migration and invasion. The regulating relationship between LINC00313 and miR-422a was investigated in PTC cells using luciferase reporter assays.
We observed that LINC00313 expression was significantly up-regulated in both PTC tissues and cell lines. Next, the results of bioinformatics analysis and luciferase reporter assays indicated that the transcription factor SP1 can bind to the promoter region of LINC00313 resulting in the overexpression of LINC00313 in PTC. Moreover, functional study revealed that knockdown of LINC00313 significantly suppressed cells proliferation, migration, invasion and EMT. Finally, our results indicated that LINC00313 functioned as an oncogene in PTC in part through serving as a competing endogenous RNA to modulate mi-422a expression.
Overall, our data demonstrated that SP1-induced LINC00313 contributed to PTC progression by via competitively binding to miR-422a, which may provide a novel therapeutic strategy for PTC.
长链非编码 RNA LINC00313（LINC00313）在多种肿瘤中失调，包括甲状腺乳头状癌（PTC）。本研究旨在进一步探讨 LINC00313 在甲状腺乳头状癌（PTC）进展中的潜在机制。
采用 RT-PCR 检测 PTC 组织和细胞系中 LINC00313 的表达。采用荧光素酶报告和染色质免疫沉淀（ChIP）实验检测 SP1 是否能结合 LINC00313 的启动子区域并激活其转录。通过下调 PTC 细胞增殖、凋亡、迁移和侵袭中 LINC00313 的表达来确定 LINC00313 的生物学功能相关性。采用荧光素酶报告实验在 PTC 细胞中研究 LINC00313 与 miR-422a 之间的调节关系。
我们观察到 LINC00313 在 PTC 组织和细胞系中均明显上调。接下来，生物信息学分析和荧光素酶报告实验的结果表明，转录因子 SP1 可以结合 LINC00313 的启动子区域，导致 PTC 中 LINC00313 的过度表达。此外，功能研究表明，下调 LINC00313 显著抑制细胞增殖、迁移、侵袭和 EMT。最后，我们的结果表明，LINC00313 在 PTC 中作为癌基因发挥作用，部分是通过作为竞争性内源性 RNA 来调节 miR-422a 的表达。
总体而言，我们的数据表明，SP1 诱导的 LINC00313 通过竞争性结合 miR-422a 促进 PTC 进展，这可能为 PTC 提供一种新的治疗策略。
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