lncRNA XIST promotes the progression of laryngeal squamous cell carcinoma by sponging miR-144 to regulate IRS1 expression (Retracted article. See vol. 46, 2021)
lncRNA XIST promotes the progression of laryngeal squamous cell carcinoma by sponging miR-144 to regulate IRS1 expression (Retracted article. See vol. 46, 2021)
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DOI：
10.3892/or.2019.7438
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发表时间：
2020-02-01
期刊：
影响因子：
4.2
通讯作者：
Wu, Xin
中科院分区：
文献类型：
--
作者：
Cui, Chang-Lei;Li, Yi-Ning;Wu, Xin
几种癌症的发生和发展与长非编码 RNA (lncRNA) X 非活性特异性转录物 (XIST) 有关。然而，XIST 在喉鳞状细胞癌 (LSCC) 中的表达模式、功能以及分子机制缺乏表征。因此，本研究旨在确定 XIST 在 LSCC 发展中的功能和推测机制。结果表明，XIST 水平在 LSCC 组织中显着较高，与晚期肿瘤淋巴结转移 (TNM) 分期和淋巴结转移的存在相关。此外，敲除XIST后，人LSCC TU212细胞的增殖、形成集落、迁移和侵袭的能力显着受到抑制，而细胞凋亡显着增加。进一步研究表明，XIST 敲低通过充当 miR-144 的内源性海绵，增加了 microRNA-144 (miR-144) 的表达。抑制 miR-144 导致 LSCC 细胞中 XIST 耗尽后介导的抑制作用部分逆转。此外，在 LSCC 细胞中，XIST 消耗显着降低了称为胰岛素受体底物 1 (IRS1) 的 miR-144 靶标。 LSCC组织中IRS1的表达与XIST的表达呈正相关。此外，XIST 的敲低通过调节 miR-144/IRS1 轴损害体内肿瘤生长。本研究表明，XIST 海绵 miR-144 调节 IRS1 表达，促进 LSCC 的进展，表明 XIST 可以作为 LSCC 治疗的推定靶点。
The initiation and development of several types of cancer have been linked to long non-coding RNA (lncRNA) X inactive-specific transcript (XIST). Yet, the pattern of expression, function, as well as the molecular mechanism underlying XIST in laryngeal squamous cell carcinoma (LSCC) lack characterization. Therefore, the present study aimed to determine the function and putative mechanism of XIST in the development of LSCC. It was revealed that the level of XIST was significantly higher in LSCC tissues that were associated with advanced Tumor-Node-Metastasis (TNM) stage and the presence of lymph node metastasis. Furthermore, the ability of human LSCC TU212 cells to proliferate, form colonies, migrate and invade was significantly suppressed, while cell apoptosis was significantly increased following knockdown of XIST. Further investigation revealed that XIST knockdown increased the expression of microRNA-144 (miR-144) by acting as an endogenous sponge of miR-144. Inhibition of miR-144 caused a partial reversal of the inhibitory effects mediated following depletion of XIST in LSCC cells. Moreover, an miR-144 target called insulin receptor substrate 1 (IRS1) was significantly decreased by XIST depletion in LSCC cells. IRS1 expression was positively correlated with XIST expression in LSCC tissues. In addition, knockdown of XIST impaired tumor growth in vivo by regulating the miR-144/IRS1 axis. The present study demonstrated that the progression of LSCC is promoted by XIST sponging miR-144 to regulate IRS1 expression, suggesting that XIST can serve as a putative target in the therapy of LSCC.