H19 Facilitates Tongue Squamous Cell Carcinoma Migration and Invasion via Sponging miR-let-7.
H19 Facilitates Tongue Squamous Cell Carcinoma Migration and Invasion via Sponging miR-let-7.
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H19 通过海绵 miR-let-7 促进舌鳞状细胞癌迁移和侵袭
DOI：
10.3727/096504018x15202945197589
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发表时间：
2019-02-05
影响因子：
3.1
通讯作者：
Liu H
中科院分区：
文献类型：
--
作者：
Kou N;Liu S;Li X;Li W;Zhong W;Gui L;Chai S;Ren X;Na R;Zeng T;Liu H
长链非编码RNA（lncRNA）H19已被描述为参与各种肿瘤的转移。然而，H19是否促进或阻碍舌鳞状细胞癌（TSCC）细胞的迁移和侵袭仍然存在争议。在这里，我们发现与邻近正常组织相比，H19在TSCC组织中的表达升高。此外，我们证明了H19的表达在转移性肿瘤中高于未转移的肿瘤。TSCC细胞表达H19的水平高于人鳞状细胞。随后，H19的缺失损害了TSCC细胞的迁移和侵袭能力。从机制上讲，我们证明了H19作为竞争性内源性RNA（ceRNA）对海绵状miRNA let-7a起作用，导致let-7a靶标增加，let-7a靶标是肿瘤转移HMGA 2的关键调节因子，其在TSCC组织和细胞系中富集。有趣的是，let-7a的抑制显著挽救了短发夹H19（shH 19）诱导的TSCC迁移和侵袭的减少。这些研究结果表明，H19/let-7a/HMGA 2/EMT轴在TSCC迁移和侵袭的调节中发挥着关键作用，这可能为TSCC提供新的治疗靶点。
The long noncoding RNA (lncRNA) H19 has been described to participate in the metastasis of various tumors. Nevertheless, whether H19 promotes or impedes tongue squamous cell carcinoma (TSCC) cell migration and invasion remains controversial. Here we found that the expression of H19 was elevated in TSCC tissues compared with adjacent normal tissues. Moreover, we demonstrated that the expression of H19 was higher in metastasized tumors compared with unmetastasized tumors. Consistently, TSCC cells express higher levels of H19 than human squamous cells. Subsequently, depletion of H19 impaired the migration and invasion abilities of TSCC cells. Mechanistically, we demonstrated that H19 functions as a competing endogenous RNA (ceRNA) to sponge miRNA let-7a, leading to an increase in a let-7a target, the key regulator of tumor metastasis HMGA2, which is enriched in TSCC tissues and cell lines. Intriguingly, inhibition of let-7a significantly rescued the short hairpin H19 (shH19)-induced decrease in TSCC migration and invasion. These findings revealed that the H19/let-7a/HMGA2/EMT axis plays a critical role in the regulation of TSCC migration and invasion, which may provide a new therapeutic target for TSCC.