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微小RNA-18b通过靶向作用调控甲状腺乳头状癌的细胞周期进程:一项实验研究

MicroRNA-18b regulates cell cycle progression in papillary thyroid carcinoma by targeting : an experimental study.

作者信息

Kim Ju-Yeon, Kim Jae-Myung, Jung Eun Jung, Son Youngsim, Kwag Seung-Jin, Park Ji-Ho, Cho Jin-Kyu, Kim Han-Gil, Kim Dong-Hwan, Jeong Sang-Ho, Jeong Chi-Young, Ju Young-Tae, Lee Young-Joon

机构信息

Department of Surgery, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju, Korea.

Department of Surgery, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwon, Korea.

出版信息

Ann Surg Treat Res. 2025 Jun;108(6):374-389. doi: 10.4174/astr.2025.108.6.374. Epub 2025 Jun 2.

Abstract

PURPOSE

Papillary thyroid carcinoma (PTC) is the most prevalent endocrine malignancy, and the global incidence has been steadily increasing over the years. Although PTC generally exhibits favorable prognosis, a subset of patients experiences aggressive progression and increased mortality. Current prognostic approaches, reliant on clinic-pathological factors, have limitations, underscoring the need for innovative biomarkers. MicroRNAs (miRs) have emerged as promising candidates due to their roles in cellular processes and cancer progression. Among them, the present study investigated the role of miR-18b in PTC, exploring its potential as a prognostic biomarker.

METHODS

Utilizing PTC cell lines (TPC1, K1), we examined miR-18b expression and its regulatory effects. The present study used web-based tools to predict the target of miR-18b and to investigate the prognostic impact of miR-18b on thyroid cancer.

RESULTS

Through a series of cell proliferation, invasion assay, gap closure, and colony formation assays, we identified that miR-18b suppresses PTC aggressiveness. Dual-luciferase assays confirmed that miR-18b directly targeted the 3'-untranslated region of and suppressed the expression of . In addition, miR-18b significantly attenuates the interaction between cyclin A or cyclin E with cyclin-dependent kinase 2 according to co-immunoprecipitation assay. Western blotting of cell cycle proteins and flow cytometry revealed miR-18b-induced cell cycle arrest and apoptosis.

CONCLUSION

Our findings underscore miR-18b's potential as a biomarker for predicting the prognosis of PTC and suggest that it functions through direct regulation of , influencing cell cycle dynamics. This study not only enhances our understanding of miR-18b in thyroid cancer but also highlights its potential in refining prognostic evaluations and therapeutic strategies.

摘要

目的

甲状腺乳头状癌(PTC)是最常见的内分泌恶性肿瘤,多年来全球发病率一直在稳步上升。虽然PTC通常预后良好,但一部分患者会出现侵袭性进展并增加死亡率。目前依赖临床病理因素的预后方法存在局限性,这凸显了对创新生物标志物的需求。微小RNA(miR)因其在细胞过程和癌症进展中的作用而成为有前景的候选者。其中,本研究调查了miR-18b在PTC中的作用,探讨其作为预后生物标志物的潜力。

方法

利用PTC细胞系(TPC1、K1),我们检测了miR-18b的表达及其调节作用。本研究使用基于网络的工具来预测miR-18b的靶标,并研究miR-18b对甲状腺癌的预后影响。

结果

通过一系列细胞增殖、侵袭试验、间隙闭合和集落形成试验,我们发现miR-18b抑制PTC的侵袭性。双荧光素酶试验证实miR-18b直接靶向 的3'-非翻译区并抑制 的表达。此外,根据免疫共沉淀试验,miR-18b显著减弱细胞周期蛋白A或细胞周期蛋白E与细胞周期蛋白依赖性激酶2之间的相互作用。细胞周期蛋白的蛋白质印迹和流式细胞术显示miR-18b诱导细胞周期停滞和凋亡。

结论

我们的研究结果强调了miR-18b作为预测PTC预后生物标志物的潜力,并表明它通过直接调节 发挥作用,影响细胞周期动态。这项研究不仅加深了我们对miR-18b在甲状腺癌中的理解,还突出了其在完善预后评估和治疗策略方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/090c/12149990/dc0abbec4a7d/astr-108-374-g001.jpg

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