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MicroRNA-592 通过靶向 ERBB3 抑制卵巢癌细胞的生长。

MicroRNA-592 Inhibits the Growth of Ovarian Cancer Cells by Targeting ERBB3.

机构信息

105762Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China.

Department of Intensive Care Medicine, Yantai Penglai Traditional Chinese Medicine Hospital, Yantai, China.

出版信息

Technol Cancer Res Treat. 2023 Jan-Dec;22:15330338231157156. doi: 10.1177/15330338231157156.

Abstract

Ovarian cancer is the most lethal gynecologic malignancy, and targeted therapy for different pathological types and molecular phenotypes is urgent to be studied. Studies have shown that MicroRNA-592 (miR-592) plays an important negative regulatory role in the occurrence of gastrointestinal malignancies, breast cancer, non-small cell lung cancer, and glioma, but the expression of miR-592 in ovarian cancer and the mechanism of action are still unclear. The expressions of miR-592 were examined by RT-PCR and Western Blot. Cell viability and migratory capacity were detected by CCK-8 and transwell assay. TargetScan (http://www.targetscan.org) was analyzed to predict potential targets of miR-592. Then Dual-luciferase reporter gene assay was performed to verify the targeting relationship between miR-592 and ERBB3. A mouse xenograft model was applied to confirm the effect of miR-592. In our study, we found that the expression of miR-592 is reduced in epithelial ovarian cancer tissues. The exogenous expression of miR-592 inhibits the proliferation, migration, and invasion in epithelial ovarian cancer tumor cells. Furthermore, the exogenous expression of miR-592 inhibits tumor growth in the nude mouse xenograft model. Therefore, miR-592 may play a role of tumor suppressor miRNA in the occurrence and development of ovarian cancer. Further experiments demonstrated that tumor-related ERBB3 is a target gene mediated by miRNA-592. The dual-luciferase reporter system was used to identify miRNA-592 target genes; qPCR and Western Blot were used to detect the expression of ERBB3. Mechanical experiments confirmed that miRNA-592 negatively regulated ERBB3. Together, these findings identify a heretofore unrecognized link between miR-592 and ERBB3 and suggest that targeting on miR-592 warrants attention as a novel and potential therapeutic strategy for ovarian cancer.

摘要

卵巢癌是最致命的妇科恶性肿瘤,针对不同病理类型和分子表型的靶向治疗亟待研究。研究表明,MicroRNA-592(miR-592)在胃肠道恶性肿瘤、乳腺癌、非小细胞肺癌和神经胶质瘤的发生中发挥重要的负调控作用,但 miR-592 在卵巢癌中的表达及其作用机制尚不清楚。通过 RT-PCR 和 Western blot 检测 miR-592 的表达。通过 CCK-8 和 Transwell 实验检测细胞活力和迁移能力。通过 TargetScan(http://www.targetscan.org)分析预测 miR-592 的潜在靶标。然后进行双荧光素酶报告基因实验验证 miR-592 与 ERBB3 的靶向关系。应用小鼠异种移植模型证实 miR-592 的作用。在本研究中,我们发现 miR-592 在卵巢上皮性癌组织中表达降低。外源性表达 miR-592 抑制上皮性卵巢癌细胞的增殖、迁移和侵袭。此外,外源性表达 miR-592 抑制裸鼠异种移植瘤的生长。因此,miR-592 可能在卵巢癌的发生发展中发挥肿瘤抑制 miRNA 的作用。进一步的实验表明,肿瘤相关的 ERBB3 是 miRNA-592 介导的靶基因。双荧光素酶报告系统用于鉴定 miRNA-592 的靶基因;qPCR 和 Western blot 用于检测 ERBB3 的表达。机械实验证实 miR-592 负调控 ERBB3。总之,这些发现确定了 miR-592 与 ERBB3 之间以前未被认识的联系,并表明针对 miR-592 值得作为卵巢癌的一种新的潜在治疗策略引起关注。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ed6/10021105/3babe1d3ec7d/10.1177_15330338231157156-fig1.jpg

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