白细胞介素-6诱导的长链非编码RNA MIR3142HG通过与人结直肠癌中的硫氧还蛋白-1和信号转导子与转录激活子3相互作用促进肿瘤发生。

IL-6-induced long noncoding RNA MIR3142HG promotes tumorigenesis by interacting with thioredoxin-1 and STAT3 in human colorectal cancer.

作者信息

Fang Daoquan, Feng Qian, Zhou Baojian, Liu Yangyang, Lian Yichu, Zhang Yihui, Yang Dichen, Liu Xintong, Shi Xiaomeng, Ni Wuhua, Jiang Lei

机构信息

Central Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.

Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, Zhejiang, China.

出版信息

Cell Mol Biol Lett. 2025 May 22;30(1):61. doi: 10.1186/s11658-025-00742-6.

DOI:10.1186/s11658-025-00742-6

PMID:40405062

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12100896/

Abstract

BACKGROUND

Colorectal cancer (CRC) is a prevalent and highly malignant neoplasm on a global scale, ranking as the second most widespread cause of cancer-associated death. Long noncoding RNAs (lncRNAs) control tumorigenic processes in CRC by modulating inflammatory signals. However, the precise mechanisms remain unknown.

METHODS

LncRNAs regulated by thioredoxin-1 (Trx-1) and interleukin (IL)-6 were identified by RNA sequencing (RNA-seq). The effect of MIR3142HG on CRC growth, migration, and invasion was assessed through methods of cell counting kit-8 (CCK-8), colony formation assay, Transwell assay, and animal experimentation, respectively. The regulation of signal transducer and activator of transcription 3 (STAT3) on the MIR3142HG promoter was verified using chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. The interaction of MIR3142HG with Trx-1 and STAT3 proteins was validated with RNA-binding protein immunoprecipitation (RIP) and RNA-pulldown experiments. Bioinformatics analysis and tissue microarray were utilized for evaluating the clinical value of MIR3142HG in CRC.

RESULTS

We identified a lncRNA, MIR3142HG, regulated by Trx-1 knockdown and IL-6 treatment. Overexpression of MIR3142HG enhanced CRC cell proliferation, migration, and invasion, while its knockdown impaired these processes. STAT3 bound to the MIR3142HG promoter and activated its transcription. Upregulated MIR3142HG acted as a scaffold for the Trx-1/STAT3 complex to inhibit the degradation of Trx-1 and phosphorylated STAT3 (p-STAT3). In situ hybridization (ISH) results of CRC tissues indicated that MIR3142HG expression was significantly elevated during the early stages of CRC. Moreover, consistent with the Cancer Genome Atlas (TCGA) dataset, high MIR3142HG expression predicted better survival.

CONCLUSIONS

Our study identified a novel lncRNA MIR3142HG, which interacts with STAT3 and Trx-1 to promote CRC progression, providing a possible diagnostic target for CRC.

摘要

背景

结直肠癌（CRC）是全球范围内一种常见且高度恶性的肿瘤，是癌症相关死亡的第二大常见原因。长链非编码RNA（lncRNA）通过调节炎症信号来控制CRC的致瘤过程。然而，确切机制仍不清楚。

方法

通过RNA测序（RNA-seq）鉴定受硫氧还蛋白-1（Trx-1）和白细胞介素（IL）-6调控的lncRNA。分别通过细胞计数试剂盒-8（CCK-8）、集落形成试验、Transwell试验和动物实验评估MIR3142HG对CRC生长、迁移和侵袭的影响。使用染色质免疫沉淀（ChIP）和双荧光素酶报告基因试验验证信号转导和转录激活因子3（STAT3）对MIR3142HG启动子的调控。通过RNA结合蛋白免疫沉淀（RIP）和RNA下拉实验验证MIR3142HG与Trx-1和STAT3蛋白的相互作用。利用生物信息学分析和组织芯片评估MIR3142HG在CRC中的临床价值。

结果

我们鉴定出一种受Trx-1敲低和IL-6处理调控的lncRNA，即MIR3142HG。MIR3142HG的过表达增强了CRC细胞的增殖、迁移和侵袭能力，而其敲低则损害了这些过程。STAT3与MIR3142HG启动子结合并激活其转录。上调的MIR3142HG作为Trx-1/STAT3复合物的支架，抑制Trx-1和磷酸化STAT3（p-STAT3）的降解。CRC组织的原位杂交（ISH）结果表明，MIR3142HG在CRC早期阶段的表达显著升高。此外，与癌症基因组图谱（TCGA）数据集一致，MIR3142HG高表达预示着更好的生存率。