长链非编码 RNA LINC01559 作为竞争性内源性 RNA 加速三阴性乳腺癌进展。

Long non-coding RNA LINC01559 serves as a competing endogenous RNA accelerating triple-negative breast cancer progression.

机构信息

Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Henan, China.

出版信息

Biomed J. 2022 Jun;45(3):512-521. doi: 10.1016/j.bj.2021.05.002. Epub 2021 May 29.

BACKGROUND

Long non-coding RNA (lncRNA) is an endogenous RNA over 200 nt in length involved in gene regulation. LINC01559 is a novel lncRNA that has been identified as a fundamental player in human cancer. However, its role in triple-negative breast cancer (TNBC) remains unknown. Here, we explored the expression, function and clinical implication of LINC01559 in TNBC.

METHODS

RNA expression was detected by qRT-PCR analysis. Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), wound healing and Transwell assays were used to test cell viability, DNA synthesis rate, migration and invasion, respectively. The competing endogenous RNA (ceRNA) axis involved in LINC01559 was determined by RNA pull-down and luciferase reporter assays. The xenograft model was used to verify the function of LINC01559 in vivo.

RESULTS

LINC01559 was significantly increased in TNBC tissues as compared to matched normal tissues, which was due to high levels of H3K4Me3 and H3K27Ac in the promoter region. Knockdown of LINC01559 inhibited TNBC cell proliferation, migration and invasion in vitro, and also retarded tumor growth and reduced lung metastasis in vivo. Mechanistically, LINC01559 served as a ceRNA that sponged miR-370-3p, miR-485-5p and miR-940, resulting in increasing the expression of a cohort of oncogenes, thus accelerating TNBC progression.

CONCLUSIONS

Our data provide a comprehensive analysis of LINC01559 in TNBC, we found that LINC01559 functioned as a carcinogenic ceRNA via sponging miRNAs. Targeting of LINC01559 may be a potential treatment for TNBC patients.

背景

长链非编码 RNA（lncRNA）是一种长度超过 200nt 的内源性 RNA，参与基因调控。LINC01559 是一种新发现的 lncRNA，已被确定为人类癌症的基本参与者。然而，它在三阴性乳腺癌（TNBC）中的作用尚不清楚。在这里，我们探讨了 LINC01559 在 TNBC 中的表达、功能和临床意义。

方法

通过 qRT-PCR 分析检测 RNA 表达。细胞计数试剂盒-8（CCK-8）、5-乙炔基-2'-脱氧尿苷（EdU）、划痕愈合和 Transwell 测定分别用于测试细胞活力、DNA 合成率、迁移和侵袭。通过 RNA 下拉和荧光素酶报告基因测定确定涉及 LINC01559 的竞争内源性 RNA（ceRNA）轴。使用异种移植模型验证 LINC01559 在体内的功能。

结果

与匹配的正常组织相比，LINC01559 在 TNBC 组织中显著增加，这是由于启动子区域中 H3K4Me3 和 H3K27Ac 水平升高所致。LINC01559 敲低抑制 TNBC 细胞在体外的增殖、迁移和侵袭，同时在体内也抑制肿瘤生长和减少肺转移。机制上，LINC01559 作为 ceRNA 可吸附 miR-370-3p、miR-485-5p 和 miR-940，从而增加一系列癌基因的表达，从而加速 TNBC 进展。