miR-191-3p 靶向调控 RGS1 抑制 CXCR4/PI3K/AKT 信号通路抑制食管癌细胞干性。
RGS1 targeted by miR-191-3p inhibited the stemness properties of esophageal cancer cells by suppressing CXCR4/PI3K/AKT signaling.
机构信息
Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100, China; Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin 300100, China; Institute of Integrative Medicine for Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100, China.
Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100, China; Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin 300100, China; Institute of Integrative Medicine for Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100, China; Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
出版信息
Acta Histochem. 2024 Oct;126(5-7):152190. doi: 10.1016/j.acthis.2024.152190. Epub 2024 Aug 21.
BACKGROUND
Esophageal cancer is one of the most common malignant tumors in the world. It is urgent to prevent the development and progression of esophageal cancer. Cancer stem cells (CSCs) were reported to have the ability to initiate tumorigenesis, and reducing the stem cell-like characteristics of tumors is an important strategy to inhibit the occurrence and development of tumors. miRNAs are key regulators of the stemness of cancer. Here, we aimed to investigate the role and regulatory mechanism of miR-191-3p in the stemness properties of esophageal cancer cells.
METHODS
Esophageal cancer cells with stable expression of miR-191-3p were established by lentivirus system. CCK-8 assay, transwell assay, wound healing assay were used to evaluate the effect of miR-191-3p on proliferation and metastasis of esophageal cancer cells. The expression of stemness-related markers (NANOG, OCT4, SOX2), ALDH activity, sphere-forming assay and subcutaneous tumor model in nude mice were performed to evaluate the stemness properties of esophageal cancer cells in vitro and in vivo. Dual-luciferase reporter assay was used to verify the molecular mechanism.
RESULT
Here we found that overexpression of miR-191-3p promoted the stemness properties of esophageal cancer cells in vitro and in vivo, including increasing esophageal cancer cell proliferation and metastasis ability, the expression of stemness-related markers NANOG, OCT4, and SOX2, ALDH activity, the number of spheres formed and tumor growth. Bioinformatic analysis and dual-luciferase assay demonstrated that regulator of G protein signaling 1 (RGS1) was the directed target gene of miR-191-3p and attenuated the promotion effect of miR-191-3p on the stemness of esophageal cancer cells. Furthermore, we found that RGS1 knockdown activated the PI3K/AKT pathway by negatively regulating CXCR4 to promote the stemness of esophageal cancer cells.
CONCLUSIONS
Our findings revealed that RGS1 targeted by miR-191-3p inhibited the stemness of esophageal cancer cells by suppressing the CXCR4/PI3K/AKT pathway, which provide potential prognostic markers and therapeutic targets in the future.
背景
食管癌是世界上最常见的恶性肿瘤之一。迫切需要预防食管癌的发生和发展。癌症干细胞（CSCs）被报道具有引发肿瘤发生的能力，降低肿瘤的干细胞样特征是抑制肿瘤发生和发展的重要策略。miRNAs 是癌症干性的关键调节因子。在这里，我们旨在研究 miR-191-3p 在食管癌干细胞干性特性中的作用和调节机制。
方法
通过慢病毒系统建立稳定表达 miR-191-3p 的食管癌细胞。CCK-8 assay、transwell assay、wound healing assay 用于评估 miR-191-3p 对食管癌细胞增殖和转移的影响。进行体外和体内实验评估食管癌细胞的干性特性，包括干细胞相关标志物（NANOG、OCT4、SOX2）的表达、ALDH 活性、球体形成实验和裸鼠皮下肿瘤模型。双荧光素酶报告实验用于验证分子机制。
结果
我们发现过表达 miR-191-3p 促进了食管癌细胞的干性特性，包括增加食管癌细胞的增殖和转移能力、干细胞相关标志物 NANOG、OCT4 和 SOX2 的表达、ALDH 活性、球体形成数量和肿瘤生长。生物信息学分析和双荧光素酶报告实验表明，G 蛋白信号调节因子 1（RGS1）是 miR-191-3p 的直接靶基因，并减弱了 miR-191-3p 对食管癌干细胞干性的促进作用。此外，我们发现 RGS1 敲低通过负调控 CXCR4 激活 PI3K/AKT 通路，从而促进食管癌干细胞的干性。
结论
我们的研究结果表明，miR-191-3p 靶向的 RGS1 通过抑制 CXCR4/PI3K/AKT 通路抑制食管癌干细胞的干性，为未来提供了潜在的预后标志物和治疗靶点。
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