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长链非编码RNA LINC00239通过吸附微小RNA-484并增强KLF12表达发挥竞争性内源性RNA的作用,从而促进结直肠癌的致癌性。

Long Non-Coding RNA LINC00239 Functions as a Competitive Endogenous RNA by Sponging microRNA-484 and Enhancing KLF12 Expression to Promote the Oncogenicity of Colorectal Cancer.

作者信息

Luo Xiaofan, Yue Meng, Li Chenguang, Sun Di, Wang Lei

机构信息

Department of Colorectal and Anal Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Nov 23;13:12067-12081. doi: 10.2147/OTT.S278582. eCollection 2020.

Abstract

BACKGROUND

() is an oncogenic long non-coding RNA in acute myeloid leukemia. We aimed to determine expression in colorectal cancer (CRC) and examine the influences of on tumor behaviors of CRC cells. Furthermore, the mechanism underlying the actions of in CRC was unveiled in detail.

MATERIALS AND METHODS

Quantitative real-time polymerase chain reaction was used to detect expression in CRC tissues and cell lines. CRC cell proliferation, apoptosis, migration, and invasion were investigated by cell counting kit-8 assays, flow cytometry, and cell migration and invasion assays, respectively. Tumor xenograft experiments were performed to evaluate the tumor growth of CRC cells in vivo. The interactions among , microRNA-484 (miR-484), and () were analyzed by bioinformatics prediction, RNA immunoprecipitation and luciferase reporter assay.

RESULTS

was upregulated in CRC tissues and cell lines. knockdown impaired CRC cell proliferation, migration, and invasion and promoted apoptosis in vitro. Additionally, deficiency inhibited CRC growth in vivo. Mechanistically, functioned as a competing endogenous RNA by directly sponging miR-484, thereby enhancing expression. Rescue experiments further corroborated that miR-484 inhibition or overexpression reversed the inhibitory actions of knockdown in CRC cells.

CONCLUSION

The LINC00239/miR-484/KLF12 pathway executed critical roles in CRC oncogenicity and may provide potential targets for CRC treatments.

摘要

背景

()是急性髓系白血病中的一种致癌长链非编码RNA。我们旨在确定其在结直肠癌(CRC)中的表达,并研究其对CRC细胞肿瘤行为的影响。此外,还详细揭示了其在CRC中作用的机制。

材料与方法

采用定量实时聚合酶链反应检测CRC组织和细胞系中的表达。分别通过细胞计数试剂盒-8检测、流式细胞术以及细胞迁移和侵袭实验研究CRC细胞的增殖、凋亡、迁移和侵袭。进行肿瘤异种移植实验以评估CRC细胞在体内的肿瘤生长情况。通过生物信息学预测、RNA免疫沉淀和荧光素酶报告基因检测分析、微小RNA-484(miR-484)和()之间的相互作用。

结果

在CRC组织和细胞系中上调。敲低在体外损害CRC细胞的增殖、迁移和侵袭并促进凋亡。此外,缺失在体内抑制CRC生长。机制上,通过直接吸附miR-484作为竞争性内源RNA发挥作用,从而增强表达。拯救实验进一步证实,抑制miR-484或过表达可逆转敲低对CRC细胞的抑制作用。

结论

LINC00239/miR-484/KLF12通路在CRC致癌过程中发挥关键作用,可能为CRC治疗提供潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8a3/7695693/6e76b03b1468/OTT-13-12067-g0001.jpg

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