Upregulated long non‑coding RNA LincIN promotes tumor progression via the regulation of nuclear factor 90/microRNA‑7/HOXB13 in esophageal squamous cell carcinoma.
Upregulated long non‑coding RNA LincIN promotes tumor progression via the regulation of nuclear factor 90/microRNA‑7/HOXB13 in esophageal squamous cell carcinoma.
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DOI：
10.3892/ijmm.2021.4911
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发表时间：
2021-05
影响因子：
5.4
通讯作者：
Wu D
中科院分区：
文献类型：
--
作者：
Tan Z;Zhou P;Zhu Z;Wang Y;Guo Z;Shen M;Xiao Y;Shen W;Wu D
据报道，长链非编码RNA LincIN 过度表达并参与乳腺癌的转移。然而，LincIN 在食管鳞状细胞癌 (ESCC) 中的表达和作用仍未解决。在本研究中，通过 RT-qPCR 检查了 ESCC 中 LincIN 的表达，并通过细胞生长、迁移和侵袭测定确定了 LincIN 在 ESCC 中的作用。此外，通过 RNA 免疫沉淀测定、RT-qPCR、双荧光素酶报告基因测定和蛋白质印迹分析检查了 LincIN 对核因子 90 (NF90) 和 microRNA/miR (miR)-7 的影响。结果显示，ESCC组织和细胞系中LincIN表达显着增加。 LincIN表达增加与浸润深度、淋巴结转移、TNM分期和不良预后呈正相关。功能分析表明，LincIN 的过度表达促进 ESCC 细胞的生长、迁移和侵袭。机理分析表明，LincIN与NF90物理结合，增强了NF90与初级miR-7（pri-miR-7）之间的结合，并进一步增强了NF90对miR-7生物发生的抑制作用。因此，LincIN 下调 ESCC 中 miR-7 的表达。 ESCC组织中miR-7的表达与LincIN的表达呈负相关。通过下调 miR-7，LincIN 增加了 miR-7 靶标 HOXB13 的表达。 miR-7 的过度表达或 HOXB13 的缺失均减弱了 LincIN 在 ESCC 细胞生长、迁移和侵袭中的促肿瘤作用。总体而言，本研究的结果表明，LincIN 过度表达，并通过调节 NF90/miR-7/HOXB13 轴在 ESCC 中发挥致癌作用。因此，LincIN 可能被证明是 ESCC 的一个有前途的预后生物标志物和治疗靶点。
Long non-coding RNA LincIN has been reported to be overexpressed and to be involved in the metastasis of breast cancer. However, the expression and role of LincIN in esophageal squamous cell carcinoma (ESCC) remain unsolved. In the present study, LincIN expression was examined in ESCC by RT-qPCR, and the roles of LincIN in ESCC were determined using cell growth, migration and invasion assays. In addition, the effects of LincIN on nuclear factor 90 (NF90) and microRNA/miR (miR)-7 were examined by RNA immunoprecipitation assay, RT-qPCR, dual-luciferase reporter assay and western blot analysis. The results revealed that LincIN expression was significantly increased in ESCC tissues and cell lines. The increased expression of LincIN was positively associated with invasion depth, lymph node metastasis, TNM stage and a poor prognosis. Functional assays revealed that the overexpression of LincIN promoted ESCC cell growth, migration and invasion. Mechanistic analysis revealed that LincIN physically bound to NF90, enhanced the binding between NF90 and primary miR-7 (pri-miR-7), and further enhanced the inhibitory effects of NF90 on miR-7 biogenesis. Therefore, LincIN downregulated miR-7 expression in ESCC. The expression of miR-7 inversely correlated with that of LincIN in ESCC tissues. By downregulating miR-7, LincIN increased the expression of HOXB13, a target of miR-7. The overexpression of miR-7 or the depletion of HOXB13 both attenuated the tumor-promoting roles of LincIN in ESCC cell growth, migration and invasion. On the whole, the findings of the present study suggest that LincIN is overexpressed and plays an oncogenic role in ESCC via the regulation of the NF90/miR-7/HOXB13 axis. Thus, LincIN may prove to be a promising prognostic biomarker and therapeutic target for ESCC.