METTL3通过PI3K/AKT和EMT信号通路对非小细胞肺癌进展的调控作用。
METTL3 regulatory TROAP can regulate the progression of non-small cell lung cancer through PI3K/AKT and EMT signaling pathway.
发表日期:2023 Aug 22
作者:
Muli Xu, Jiankun Yu, Xiaoxiao Liu, Wanting Jia, Yu Duan, Di Ma, Jiaxuan Ma, Wanyang Lei, Wenlin Tai
来源:
Cellular & Molecular Immunology
摘要:
TROAP与trophinin和bystin相互作用,在胚胎着床过程中发挥关键作用。在有丝分裂过程中,TROAP对纺锤体组装和中心体完整性至关重要。已有研究表明,TROAP在多种癌症中促进肿瘤发生。我们进行了这项研究,评估TROAP在非小细胞肺癌中的生物学和临床意义。收集了48对肺腺癌(LUAD)组织和癌旁组织。通过RT-qPCR、Western blot和免疫组化分析,检测了LUAD细胞系和对照细胞系中TROAP的RNA和蛋白质表达。构建了TROAP沉默和过表达载体,并转染到肺癌细胞中。使用CCK-8、Transwell和划痕愈合实验评估了细胞的生存能力、迁移和侵袭能力。通过Western blot确定了PI3K/AKT和EMT信号通路以及METTL3的表达情况。我们发现TROAP在非小细胞肺癌组织和细胞系中富集。相比于对照组,在非小细胞肺癌中,TROAP沉默抑制了细胞的增殖、迁移和侵袭。机制分析表明,TROAP激活了PI3K/AKT和EMT信号通路。在一定程度上,TROAP受METTL3的调节。总之,TROAP通过PI3K/AKT和EMT信号通路促进了非小细胞肺癌的进展,并且TROAP可能被视为非小细胞肺癌治疗的一个新靶点。© 2023版权归作者独家许可Springer Science+Business Media, LLC, part of Springer Nature所有。
TROAP, interacts with trophinin and bystin, polys a key role in embryo implantation. TROAP is required for spindle assembly and centrosome integrity during the mitosis. TROAP has been described to promote tumorigenesis in a diverse range of cancer. We performed this study to assess the biological and clinical significance of TROAP in Non-small cell lung cancer. Forty-eight pairs of lung adenocarcinoma (LUAD) tissues and paraneoplastic tissues were collected. RT-qPCR, western bolt and immunohistochemistry assay was used to test TROAP RNA and protein expression not in LUAD tissues and paraneoplastic tissues but in LUAD cell lines and control cell lines. TROAP knockdown and overexpression vector were constructed and transfected into lung cancer cells. CCK-8, transwell, and wound healing assays were used to assess cell viability, migration, and invasion. The expression of PI3K/AKT and EMT signaling proteins and METTL3 were determined by western blot. We found the TROAP was enriched in NSCLC tissues and cell lines. TROAP knockdown inhibited cell proliferation, migration, invasion compared with control group in NSCLC. Mechanism analysis revealed that TROAP activated PI3K/AKT and EMT signaling pathway. To a certain extent, TROAP was regulated by METTL3. In a word, TROAP accelerated the progression of NSCLC through PI3K/AKT and EMT pathway, and TROAP might be considered as a novel target for NSCLC therapy.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.