Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
Key Laboratory of Cancer Prevention and Therapy, Tianjin Tumor Hospital, Tianjin, China.
Thorac Cancer. 2024 Sep;15(26):1889-1896. doi: 10.1111/1759-7714.15415. Epub 2024 Aug 4.
Lung cancer is one of the major threats to human life worldwide. MiR-190 has been found to perform essential roles in multiple cancer progression; however, there have been no studies focused on its function and underlying regulatory mechanism in lung cancer.
The miR-190 expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The cell functional experiments, including cell counting kit-8 (CCK-8), colony formation and transwell assay were conducted in vitro, as well as animal experiments performed in vivo. The regulation and potential binding sites of CBX4 on miR-190 were predicted by TCGA data set and JASPAR website and verified by ChIP assay and dual-luciferase reporter assay. The prospects binding site of miR-190-3p on CBX4 3'UTR region was predicted by StarBase and verified by dual-luciferase reporter assay.
MiR-190 was decreased in lung cancer cells. The overexpression of miR-190 had no effects on cell proliferation, but significantly inhibited cancer metastasis both in vitro and in vivo. Moreover, miR-190 expression could be transcriptionally inhibited by CBX4, and CBX4 was the direct target of miR-190-3p.
MiR-190 served as a cancer metastasis inhibitor in lung cancer and formed a regulatory loop with CBX4. These findings provided emerging insights into therapeutic targets and strategies for metastatic lung cancer.
肺癌是全球范围内威胁人类生命的主要疾病之一。miR-190 已被发现于多种癌症的进展中发挥重要作用，但目前尚无研究关注其在肺癌中的功能和潜在调控机制。
采用实时定量聚合酶链反应（RT-qPCR）检测 miR-190 的表达。通过细胞计数试剂盒-8（CCK-8）、集落形成和 Transwell 实验进行体外细胞功能实验，以及体内动物实验。通过 TCGA 数据集和 JASPAR 网站预测 CBX4 对 miR-190 的调控及潜在结合位点，并通过 ChIP 实验和双荧光素酶报告基因实验进行验证。通过 StarBase 预测 miR-190-3p 与 CBX4 3'UTR 区域的结合位点，并通过双荧光素酶报告基因实验进行验证。
miR-190 在肺癌细胞中表达下调。miR-190 的过表达对细胞增殖没有影响，但显著抑制了体外和体内的癌症转移。此外，CBX4 可转录抑制 miR-190 的表达，而 CBX4 是 miR-190-3p 的直接靶基因。
miR-190 作为肺癌的癌症转移抑制剂，与 CBX4 形成调节环路。这些发现为转移性肺癌的治疗靶点和策略提供了新的见解。
