Long non-coding RNA SOCS2-AS1 inhibits gastric cancer progression via the miR-324-3p/GRIK3 axis: a mechanistic study.

IF 2.8 3区 医学 Q3 ONCOLOGY
Houyun Zhang, Zhisheng Xia, Yuan Xu, Xiaolan Ouyang
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Abstract

Background: Gastric cancer (GC) remains a formidable threat to global health. Although SOCS2-AS1 is abnormally expressed in various cancers, its precise function and operational mechanisms in the context of GC have not been fully elucidated.

Methods: This study collected 102 pairs of GC and adjacent normal tissue samples and cultured multiple GC cell lines. SOCS2-AS1, miR-324-3p, and glutamate ionotropic receptor kainate type subunit 3 (GRIK3) expression were detected by qRT-PCR. Bioinformatics analysis was performed using databases such as GEPIA and Starbase. Functional experiments including CCK-8 assay and Transwell assay were conducted to evaluate cellular functions. Subcellular localization was determined using nuclear-cytoplasmic separation technology. Direct molecular interactions were validated via dual luciferase reporter assays.

Results: The downregulation of SOCS2-AS1 in GC tissues and cell lines is significantly associated with an unfavorable patient prognosis. Overexpression of SOCS2-AS1 markedly suppressed GC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) progression. Mechanistic studies revealed that SOCS2-AS1 targets miR-324-3p. and re-expression experiments confirmed its ability to reverse the anti-cancer effects of SOCS2-AS1. GRIK3 was identified as a direct downstream target of miR-324-3p. Ultimately, SOCS2-AS1 exerts its tumor-suppressive function through the miR-324-3p/GRIK3 axis.

Conclusion: This research identifies SOCS2-AS1 as an anti-cancer lncRNA in GC and uncovers its mechanism of action via the SOCS2-AS1/miR-324-3p/GRIK3 axis in suppressing tumor progression. Thus, SOCS2-AS1 may serve as a potential diagnostic biomarker and therapeutic target for GC.

长链非编码RNA SOCS2-AS1通过miR-324-3p/GRIK3轴抑制胃癌进展:一项机制研究
背景:胃癌(GC)仍然是对全球健康的巨大威胁。尽管SOCS2-AS1在多种癌症中异常表达,但其在GC背景下的确切功能和运作机制尚未完全阐明。方法:收集102对胃癌及邻近正常组织标本,培养多株胃癌细胞系。采用qRT-PCR检测SOCS2-AS1、miR-324-3p和谷氨酸嗜离子受体kainate型亚单位3 (GRIK3)的表达。使用GEPIA和Starbase等数据库进行生物信息学分析。功能实验包括CCK-8法和Transwell法评价细胞功能。亚细胞定位采用核细胞质分离技术。通过双荧光素酶报告基因测定验证了直接分子相互作用。结果:GC组织和细胞系中SOCS2-AS1的下调与患者预后不良显著相关。过表达SOCS2-AS1可显著抑制胃癌细胞的增殖、迁移、侵袭和上皮-间质转化(EMT)进展。机制研究表明SOCS2-AS1靶向miR-324-3p。再表达实验证实其能够逆转SOCS2-AS1的抗癌作用。GRIK3被确定为miR-324-3p的直接下游靶点。最终,SOCS2-AS1通过miR-324-3p/GRIK3轴发挥其肿瘤抑制功能。结论:本研究确定了SOCS2-AS1在胃癌中是一种抗癌lncRNA,并揭示了其通过SOCS2-AS1/miR-324-3p/GRIK3轴抑制肿瘤进展的作用机制。因此,SOCS2-AS1可能作为GC的潜在诊断生物标志物和治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.70
自引率
15.60%
发文量
362
审稿时长
3 months
期刊介绍: World Journal of Surgical Oncology publishes articles related to surgical oncology and its allied subjects, such as epidemiology, cancer research, biomarkers, prevention, pathology, radiology, cancer treatment, clinical trials, multimodality treatment and molecular biology. Emphasis is placed on original research articles. The journal also publishes significant clinical case reports, as well as balanced and timely reviews on selected topics. Oncology is a multidisciplinary super-speciality of which surgical oncology forms an integral component, especially with solid tumors. Surgical oncologists around the world are involved in research extending from detecting the mechanisms underlying the causation of cancer, to its treatment and prevention. The role of a surgical oncologist extends across the whole continuum of care. With continued developments in diagnosis and treatment, the role of a surgical oncologist is ever-changing. Hence, World Journal of Surgical Oncology aims to keep readers abreast with latest developments that will ultimately influence the work of surgical oncologists.
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