环状 RNA hsa_circ_0110389 通过海绵吸附 miR-127-5p 和 miR-136-5p 而上调 SORT1 促进胃癌进展。

Circular RNA hsa_circ_0110389 promotes gastric cancer progression through upregulating SORT1 via sponging miR-127-5p and miR-136-5p.

机构信息

Department of Oncology, Guangzhou Key Laboratory of Enhanced Recovery after Abdominal Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, 510700, Guangzhou, China.

Medical Oncology Department, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou Medical University, 510095, Guangzhou, China.

出版信息

Cell Death Dis. 2021 Jun 23;12(7):639. doi: 10.1038/s41419-021-03903-5.

DOI:10.1038/s41419-021-03903-5

PMID:34162830

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8222372/

Abstract

Increasing studies have found that circular RNAs (circRNAs) are aberrantly expressed and play important roles in the occurrence and development of human cancers. However, the function of circRNAs on environmental carcinogen-induced gastric cancer (GC) progression remains poorly elucidated. In the present study, hsa_circ_0110389 was identified as a novel upregulated circRNA in malignant-transformed GC cells through RNA-seq, and subsequent quantitative real-time PCR verified that hsa_circ_0110389 was significantly increased in GC tissues and cells. High hsa_circ_0110389 expression associates with advanced stages of GC and predicts poor prognosis. Knockdown and overexpression assays demonstrated that hsa_circ_0110389 regulates proliferation, migration, and invasion of GC cells in vitro. In addition, hsa_circ_0110389 was identified to sponge both miR-127-5p and miR-136-5p and SORT1 was validated as a direct target of miR-127-5p and miR-136-5p through multiple mechanism assays; moreover, hsa_circ_0110389 sponged miR-127-5p/miR-136-5p to upregulate SORT1 expression and hsa_circ_0110389 promoted GC progression through the miR-127-5p/miR-136-5p-SORT1 pathway. Finally, hsa_circ_0110389 knockdown suppressed GC growth in vivo. Taken together, our findings firstly identify the role of hsa_circ_0110389 in GC progression, which is through miR-127-5p/miR-136-5p-SORT1 pathway, and our study provides novel insight for the identification of diagnostic/prognostic biomarkers and therapeutic targets for GC.

摘要

越来越多的研究发现，环状 RNA（circRNA）表达异常，并在人类癌症的发生和发展中发挥重要作用。然而，circRNA 在环境致癌物诱导的胃癌（GC）进展中的作用仍不清楚。在本研究中，通过 RNA-seq 发现 hsa_circ_0110389 是恶性转化的 GC 细胞中一种新型上调的 circRNA，随后的定量实时 PCR 验证 hsa_circ_0110389 在 GC 组织和细胞中显著增加。高 hsa_circ_0110389 表达与 GC 的晚期阶段相关，并预测预后不良。敲低和过表达实验表明，hsa_circ_0110389 调节 GC 细胞的体外增殖、迁移和侵袭。此外，hsa_circ_0110389 被鉴定为 miR-127-5p 和 miR-136-5p 的海绵体，SORT1 通过多种机制实验被验证为 miR-127-5p 和 miR-136-5p 的直接靶标；此外，hsa_circ_0110389 通过海绵 miR-127-5p/miR-136-5p 上调 SORT1 表达，hsa_circ_0110389 通过 miR-127-5p/miR-136-5p-SORT1 通路促进 GC 进展。最后，hsa_circ_0110389 的敲低抑制了体内 GC 的生长。总之，我们的研究结果首次确定了 hsa_circ_0110389 在 GC 进展中的作用，是通过 miR-127-5p/miR-136-5p-SORT1 通路，我们的研究为 GC 的诊断/预后标志物和治疗靶点的鉴定提供了新的见解。