长非编码 RNA ESCCAL-1/miR-590/LRP6 信号通路参与食管鳞癌细胞的进展。

Long non-coding RNA ESCCAL-1/miR-590/LRP6 signaling pathway participates in the progression of esophageal squamous cell carcinoma.

机构信息

Department of translational Medical Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

出版信息

Cancer Med. 2023 Jan;12(1):445-458. doi: 10.1002/cam4.4915. Epub 2022 Jun 2.

BACKGROUND

Long non-coding RNAs (lncRNAs) have critical functions within esophageal squamous cell carcinoma (ESCC). However, the function and mechanism underlying ESCC-associated lncRNA-1 (ESCCAL-1) in ESCC tumorigenesis have not been well clarified.

METHODS

ESCCAL-1, miR-590 and LRP6 were quantified using qRT-PCR. Cell viability, migration and invasion abilities were measured using CCK-8 assay and transwell assays. The protein pression was determined with western blot assay. The xenograft model assays were used to examine the impact of ESCCAL-1 on tumorigenic effect in vivo. Direct relationships among ESCCAL-1, miR-590 and LRP6 were confirmed using dual-luciferase reporter assays.

RESULTS

The present work discovered the ESCCAL-1 up-regulation within ESCC. Furthermore, ESCCAL-1 was found to interact with miR-590 and consequently restrict its expression. Functionally, knocking down ESCCAL-1 or over-expressing miR-590 hindered ESCC cell growth, invasion, and migration in vitro. Moreover, inhibition of miR-590 could reverse the effect of knockdown of ESCCAL-1 on cells. Importantly, it was confirmed that LRP6 was miR-590's downstream target and LRP6 over-expression also partly abolished the role of miR-590 overexpression in ESCC cells.

CONCLUSION

We have uncovered a novel regulatory network comprising aberrant interaction of ESCCAL-1/miR-590/LRP6 participated in ESCC progression.

背景

长链非编码 RNA（lncRNA）在食管鳞状细胞癌（ESCC）中具有重要功能。然而，ESCC 相关 lncRNA-1（ESCCAL-1）在 ESCC 肿瘤发生中的功能和机制尚未得到充分阐明。

方法

使用 qRT-PCR 定量检测 ESCCAL-1、miR-590 和 LRP6。使用 CCK-8 测定法和 Transwell 测定法测定细胞活力、迁移和侵袭能力。使用 Western blot 测定法测定蛋白质表达。使用异种移植模型测定法研究 ESCCAL-1 对体内致瘤作用的影响。使用双荧光素酶报告基因测定法证实 ESCCAL-1、miR-590 和 LRP6 之间的直接关系。

结果

本研究发现 ESCC 中 ESCCAL-1 的上调。此外，发现 ESCCAL-1 与 miR-590 相互作用，从而限制其表达。功能上，敲低 ESCCAL-1 或过表达 miR-590 可抑制 ESCC 细胞在体外的生长、侵袭和迁移。此外，抑制 miR-590 可逆转敲低 ESCCAL-1 对细胞的作用。重要的是，证实 LRP6 是 miR-590 的下游靶标，LRP6 过表达也部分消除了 miR-590 过表达在 ESCC 细胞中的作用。