Alanazi Ashwaq, Barui Ayan K, Mohieldin Ashraf M, Gupta Ankan, Ramchandran Ramani, Nauli Surya M
Department of Biomedical and Pharmaceutical Sciences, Chapman University, Irvine, CA, United States.
Department of Pharmacology and Toxicology, Umm Al-Qura University, Makkah, Saudi Arabia.
Front Cell Dev Biol. 2024 Aug 29;12:1397931. doi: 10.3389/fcell.2024.1397931. eCollection 2024.
Emerging evidence suggests a significant contribution of primary cilia to cell division and proliferation. MicroRNAs, especially miR-17, contribute to cell cycle regulation and proliferation. Recent investigations have highlighted the dysregulated expression of miR-17 in various malignancies, underlining its potential role in cancer. However, the correlation between primary cilia and miR-17 has yet to be fully elucidated. The present study examines the presence of miR-17 in primary cilia. The miR-17 expression is studied in selected ciliary protein knockdown cells. Using hybridization (ISH), we identified the subcellular localization of miR-17 in both cilium and cell body. We confirmed the importance of miR-17, progesterone receptor membrane component-2 (PGRMC2), and monosialodihexosylganglioside (GM3S) in cilia formation, as shown by the significant reduction in cilia and cilia length in knockdown cells compared to control. We also demonstrated the involvement of PGRMC2, GM3S, polycystin-2 (PKD2), and miR-17 in cellular proliferation and cell growth. Our studies revealed a hyperproliferative effect in the knockdown cells compared to control cells, suggesting the regulatory roles of PGRMC2/GM3S/PKD2/miR-17 in promoting cell proliferation. Overall, our studies conclude that ciliary proteins are involved in cell division and proliferation. We further hypothesize that primary cilia can serve as compartments to store and control genetic materials, further implicating their complex involvement in cellular processes.
新出现的证据表明，初级纤毛对细胞分裂和增殖有重大贡献。微小RNA，尤其是miR-17，参与细胞周期调控和增殖。最近的研究突出了miR-17在各种恶性肿瘤中表达失调，突显了其在癌症中的潜在作用。然而，初级纤毛与miR-17之间的相关性尚未完全阐明。本研究检测了初级纤毛中miR-17的存在情况。在选定的纤毛蛋白敲低细胞中研究了miR-17的表达。通过原位杂交（ISH），我们确定了miR-17在纤毛和细胞体中的亚细胞定位。我们证实了miR-17、孕激素受体膜组分2（PGRMC2）和单唾液酸二己糖神经节苷脂（GM3S）在纤毛形成中的重要性，与对照相比，敲低细胞中的纤毛和纤毛长度显著减少就证明了这一点。我们还证明了PGRMC2、GM3S、多囊蛋白-2（PKD2）和miR-17参与细胞增殖和细胞生长。我们的研究显示，与对照细胞相比，敲低细胞中有过度增殖效应，提示PGRMC2/GM3S/PKD2/miR-17在促进细胞增殖中具有调节作用。总体而言，我们的研究得出结论，纤毛蛋白参与细胞分裂和增殖。我们进一步推测，初级纤毛可作为储存和控制遗传物质的区室，进一步表明它们在细胞过程中有着复杂的参与情况。
