Long non-coding RNA AC010457.1 promotes the growth and EMT of gastric cancer via the PI3K/AKT axis

IF 2.9 4区 医学 Q2 PATHOLOGY Pathology, research and practice Pub Date : 2024-10-10 DOI:10.1016/j.prp.2024.155646
Chenyu Qian , Yu Chen , Zihao Zhao , Yilin Hu , Jianfeng Yi , Shun Chen , Jiancheng He , Junjie Chen , Wanjiang Xue
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Abstract

Gastric cancer (GC) is a malignancy with a relatively high mortality rate. This study aimed to ascertain the prognostic significance of long non-coding RNA (lncRNA) AC010457.1 in GC and elucidate its role in disease progression. The Cancer Genome Atlas (TCGA) database was used to screen the prognosis-associated differentially expressed lncRNAs in GC patients. Kaplan-Meier curves, univariate and multivariate Cox regression analyses were applied to assess the prognostic significance of AC010457.1. In vitro and in vivo functional assays were performed to evaluate the effects of AC010457.1 on cellular proliferation and metastasis. Mechanistic investigations, including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Western blotting (WB), Immunofluorescence (IF), and Immunohistochemistry (IHC), were used to explore the signaling pathways activated by AC010457.1. We demonstrated that AC010457.1 was abnormally upregulated in GC tissues, and that this aberrant upregulation was associated with a poor prognosis for GC patients. The functional experiments proved that the downregulated of AC010457.1 hindered GC cell proliferation, migration, and invasive potential. Furthermore, KEGG analysis revealed a significant association between AC010457.1 and the PI3K/AKT signaling pathway, which was further corroborated by WB analysis. Rescue experiments provided additional confirmation that AC010457.1 regulated PI3K/AKT promote GC proliferation, migration, and epithelial-mesenchymal transition (EMT). Collectively, our findings suggest that AC010457.1 overexpression serves as a distinct prognostic risk factor in GC and may represent a promising therapeutic target for the treatment of this malignancy.
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长非编码 RNA AC010457.1 通过 PI3K/AKT 轴促进胃癌的生长和 EMT。
胃癌(GC)是一种死亡率相对较高的恶性肿瘤。本研究旨在确定长非编码RNA(lncRNA)AC010457.1在胃癌中的预后意义,并阐明其在疾病进展中的作用。癌症基因组图谱(TCGA)数据库用于筛选GC患者中与预后相关的差异表达lncRNA。应用Kaplan-Meier曲线、单变量和多变量Cox回归分析评估了AC010457.1的预后意义。体外和体内功能测试评估了 AC010457.1 对细胞增殖和转移的影响。机理研究包括京都基因和基因组百科全书(KEGG)通路分析、免疫印迹(WB)、免疫荧光(IF)和免疫组织化学(IHC),用于探索AC010457.1激活的信号通路。我们发现 AC010457.1 在 GC 组织中异常上调,而这种异常上调与 GC 患者的不良预后有关。功能实验证明,AC010457.1的下调阻碍了GC细胞的增殖、迁移和侵袭潜力。此外,KEGG分析显示AC010457.1与PI3K/AKT信号通路有显著关联,WB分析进一步证实了这一点。复苏实验进一步证实,AC010457.1调节PI3K/AKT促进了GC的增殖、迁移和上皮-间质转化(EMT)。总之,我们的研究结果表明,AC010457.1 的过表达是 GC 的一个独特的预后风险因素,可能是治疗这种恶性肿瘤的一个有希望的治疗靶点。
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来源期刊
CiteScore
5.00
自引率
3.60%
发文量
405
审稿时长
24 days
期刊介绍: Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.
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