LINC01224 通过靶向 miR-485-5p/MYO6 轴促进结直肠癌进展。

LINC01224 promotes colorectal cancer progression through targeting miR-485-5p/MYO6 axis.

机构信息

Department of General Surgery, the First Hospital of Hebei Medical University, No.89 Donggang Road, Shijiazhuang, Hebei, China.

Department of Medical Service, the First Hospital of Hebei Medical University, Shijiazhuang, China.

出版信息

World J Surg Oncol. 2021 Sep 17;19(1):281. doi: 10.1186/s12957-021-02389-x.

BACKGROUND

Long noncoding RNAs (lncRNAs) are related to colorectal cancer (CRC) development. However, the role and mechanism of lncRNA LINC01224 in CRC development are largely unknown.

METHODS

LINC01224, Yin Yang 1 (YY1), microRNA (miR)-485-5p, and myosins of class VI (MYO6) levels were examined using quantitative reverse transcription polymerase chain reaction and western blotting. Functional analyses were processed through CCK-8, colony formation, flow cytometry, transwell, and xenograft analyses. Dual-luciferase reporter, chromatin immunoprecipitation (ChIP), RNA immunoprecipitation, and pull-down assays were conducted to analyze the binding interaction.

RESULTS

LINC01224 abundance was elevated in CRC tissue samples and cell lines. Elevated LINC01224 might indicate the lower 5-year overall survival in 52 CRC patients. LINC01224 was upregulated via the transcription factor YY1. LINC01224 knockdown restrained CRC cell proliferation, migration, and invasion and increased apoptosis. MiR-485-5p was sponged by LINC01224, and miR-485-5p downregulation relieved the influence of LINC01224 interference on CRC progression. MYO6 was targeted via miR-485-5p and regulated via LINC01224/miR-485-5p axis. MiR-485-5p overexpression suppressed CRC cell proliferation, migration, and invasion and facilitated apoptosis. MYO6 upregulation mitigated the role of miR-485-5p. LINC01224 knockdown decreased xenograft tumor growth.

CONCLUSION

YY1-induced LINC01224 regulates CRC development via modulating miR-485-5p/MYO6 axis.

背景

长链非编码 RNA（lncRNA）与结直肠癌（CRC）的发展有关。然而，lncRNA LINC01224 在 CRC 发展中的作用和机制在很大程度上尚不清楚。

方法

采用定量逆转录聚合酶链反应和 Western blot 检测 LINC01224、Yin Yang 1（YY1）、微小 RNA（miR）-485-5p 和肌球蛋白 VI 类（MYO6）的水平。通过 CCK-8、集落形成、流式细胞术、Transwell 和异种移植分析进行功能分析。通过双荧光素酶报告、染色质免疫沉淀（ChIP）、RNA 免疫沉淀和下拉分析来分析结合相互作用。

结果

LINC01224 在 CRC 组织样本和细胞系中表达上调。52 例 CRC 患者中，LINC01224 升高提示 5 年总生存率降低。LINC01224 是通过转录因子 YY1 上调的。LINC01224 敲低抑制 CRC 细胞增殖、迁移和侵袭，增加细胞凋亡。LINC01224 可吸附 miR-485-5p，LINC01224 干扰对 CRC 进展的影响可因 miR-485-5p 下调而缓解。MYO6 是 miR-485-5p 的靶标，并受 LINC01224/miR-485-5p 轴调控。miR-485-5p 过表达抑制 CRC 细胞增殖、迁移和侵袭，促进细胞凋亡。MYO6 上调减轻了 miR-485-5p 的作用。LINC01224 敲低可减少异种移植肿瘤生长。