Background. Long intergenic noncoding RNA1184 (linc01184) has been recently discovered; however, its role in human diseases is limited to date. The present study is aimed at investigating the expression pattern and mechanism of linc01184 in colorectal cancer (CRC) tumorigenesis. Methods. The expression of linc01184 in CRC tissues and cell lines was compared with that in normal controls. The functions of linc01184 in CRC cells were identified by overexpression and small interfering RNA (siRNA) approaches in vitro. Meanwhile, the target gene prediction software, luciferase reporter, RNA pull-down, and western blotting assays were used to analyze the oncogenic mechanism. Results. We found that linc01184 was obviously upregulated in CRC tissues and cells when compared to normal controls, and its upregulation had a positive association with the CRC progression. linc01184 knockdown significantly suppressed CRC cell proliferation and invasion and promoted apoptosis. Besides, linc01184 acted as a competitive endogenous RNA (ceRNA) by directly binding to microRNA-331 (miR-331), and its overexpression resulted in notable increases of human epidermal growth factor receptor 2 (HER2), phosphorylated Ser/Thr kinases (p-Akt), and extracellular regulated protein kinase 1/2 (p-ERK1/2) at posttranscriptional levels in CRC cells, which were antagonized by miR-331. Conclusions. The findings reveal for the first time that linc01184 is an enhancer for the proliferation and invasion of CRC by functioning as a ceRNA through the linc01184-miR-331-HER2-p-Akt/ERK1/2 pathway regulatory network.

中文翻译：

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长基因间非编码 RNA1184 (linc01184) 在结直肠癌中的作用、功能和机制

背景。最近发现了长基因间非编码 RNA1184 (linc01184)；然而，迄今为止，它在人类疾病中的作用是有限的。本研究旨在研究 linc01184 在结直肠癌 (CRC) 肿瘤发生中的表达模式和机制。方法。将 linc01184 在 CRC 组织和细胞系中的表达与正常对照进行比较。linc01184 在 CRC 细胞中的功能通过体外过表达和小干扰 RNA (siRNA) 方法进行鉴定。同时，利用靶基因预测软件、荧光素酶报告基因、RNA pull-down、western blotting等方法分析其致癌机制。结果. 我们发现 linc01184 在 CRC 组织和细胞中与正常对照相比明显上调，其上调与 CRC 进展呈正相关。linc01184 敲低显着抑制 CRC 细胞增殖和侵袭并促进细胞凋亡。此外，linc01184 通过直接与 microRNA-331 (miR-331) 结合充当竞争性内源性 RNA (ceRNA)，其过表达导致人表皮生长因子受体 2 (HER2)、磷酸化 Ser/Thr 激酶 (p -Akt) 和 CRC 细胞转录后水平的细胞外调节蛋白激酶 1/2 (p-ERK1/2)，它们被 miR-331 拮抗。结论. 研究结果首次揭示了 linc01184 通过 linc01184-miR-331-HER2-p-Akt/ERK1/2 通路调控网络作为 ceRNA 发挥作用，从而增强了 CRC 的增殖和侵袭。