PIWIL2 通过与 miR-146a-3p 相互作用,抑制了甲状腺癌的发展。
PIWIL2 restrains the progression of thyroid cancer via interaction with miR-146a-3p.
发表日期:2023 Aug 29
作者:
Xiaoxiao Lu, Qingyun Zhu, Hong Du, Mingjun Gu, Xiangqi Li
来源:
Cellular & Molecular Immunology
摘要:
PIWIL2的经典作用是通过结合piRNA来调节生殖,但近年来其与肿瘤相关的功能引起了越来越多的关注。本研究旨在探索其在甲状腺癌(TC)进展中的作用。首先,我们测量和分析了TC组织和相邻组织以及几种TC细胞系中PIWIL2和miR-146a-3p的水平。我们通过生存率证明了PIWIL2和miR-146a-3p的临床意义。基于这些结果,我们选择了TPC-1和KTC-3细胞系进行细胞实验。我们分别用PIWIL2慢病毒、PIWIL2 siRNA、miR-146a-3p模拟物或miR-146a-3p抑制物处理这些细胞系,并测量了细胞增殖、细胞周期、凋亡、迁移和侵袭。我们使用PCR和Western blot定量PIWIL2的mRNA和蛋白水平,使用荧光素酶报告基因实验和RNA结合蛋白免疫沉淀来探索miR-146a-3p和PIWIL2之间的关系。最后,我们建立了一个裸鼠移植瘤模型,以证实miR-146a-3p/PIWIL2轴对TC进展的影响。我们发现PIWIL2和miR-146a-3p在TC组织中表达变化相反,并且PIWIL2通过吸附miR-146a-3p充当“海绵”。上调PIWIL2减缓了TPC-1和KTC-3细胞的增殖、转移和细胞周期进展,但加速了TC细胞的凋亡,而miR-146a-3p表现出相反的效果。最后,过表达PIWIL2抑制了裸鼠中TC的进展,这可以通过增加miR-146a-3p的表达来逆转。另一方面,抑制PIWIL2则促进了裸鼠中TC的进展,这可以通过抑制miR-146a-3p来逆转。PIWIL2可能通过吸附miR-146a-3p抑制TC的进展,为TC的早期治疗、复发治疗和转移治疗提供了新的见解。© 2023. BioMed Central Ltd., part of Springer Nature.
The classical role of PIWIL2 is to regulate reproduction by binding to piRNA, but its tumor-related function has received increasing attention in recent years. This study aims to explore its role in the progression of thyroid cancer (TC).First, we measured and analyzed the levels of PIWIL2 and miR-146a-3p in TC tissue and adjacent tissues as well as several TC cell lines. We demonstrated the clinical significance of PIWIL2 and miR-146a-3p through the survival rate. Based on these results, we selected TPC-1 and KTC-3 cell lines for our cell experiments. We treated these cell lines with PIWIL2 lentivirus, PIWIL2 siRNA, miR-146a-3p mimic, or miR-146a-3p inhibitor and measured cell proliferation, cell cycle, apoptosis, migration, and invasion. We used PCR and Western blot to quantify the mRNA and protein levels of PIWIL2, while we used luciferase reporter assay and RNA binding protein immunoprecipitation to explore the relationship between miR-146a-3p and PIWIL2. Finally, we developed a xenograft tumor model to confirm the effects of the miR-146a-3p/PIWIL2 axis on TC progression in vivo.We identified that PIWIL2 and miR-146a-3p exhibit opposite expression alterations in TC tissues and that PIWIL2 serves as a 'sponge' by adsorbing miR-146a-3p. Up-regulating PIWIL2 decelerated the proliferation, metastasis, and cell cycle progression of TPC-1 and KTC-3 cells, but accelerated the apoptosis of TC cells, while miR-146a-3p exhibited opposite effects. Finally, overexpressing PIWIL2 restrained the progression of TC in nude mice, which can be reversed by increasing miR-146a-3p expression. Inhibiting PIWIL2, on the other hand, promoted the progression of TC in vivo, which can be reversed by inhibiting miR-146a-3p.PIWIL2 may inhibit the progression of TC by sponging miR-146a-3p, providing new insights into the early treatment, recrudescence treatment, and metastasis treatment of TC.© 2023. BioMed Central Ltd., part of Springer Nature.