长链非编码RNA长链基因间非蛋白编码RNA 173通过调控microRNA-765/Gremlin 1通路参与鼻咽癌的进展。

IF 2.7 4区 医学 Q3 TOXICOLOGY Human & Experimental Toxicology Pub Date : 2023-01-01 DOI:10.1177/09603271231172921
Dan Wang, Heng Jiang
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引用次数: 0

摘要

背景:长基因间非蛋白编码RNA 173 (LINC00173)在多种癌症中发挥重要作用。然而,其在鼻咽癌(NPC)中的作用和表达尚未被研究。本研究探讨了其对鼻咽癌恶性特征的影响,并阐明了LINC00173在鼻咽癌进展中的潜在分子机制。方法:采用实时定量逆转录pcr (qRT-PCR)和免疫印迹法检测鼻咽癌细胞和组织中LINC00173、microRNA-765 (miR-765)和Gremlin 1 (GREM1)的表达。细胞计数试剂盒-8 (CCK8)、菌落形成和伤口愈合实验分别评估鼻咽癌细胞的增殖、生长和迁移。通过异种移植肿瘤实验评估鼻咽癌细胞在体内的肿瘤生长情况。此外,通过生物信息学分析、荧光素酶报告基因和RNA免疫沉淀芯片检测,研究了miR-765、LINC00173和GREM1之间的相互作用。结果:LINC00173在鼻咽癌细胞系和组织中表达上调。功能实验发现其下调可抑制鼻咽癌细胞的增殖、生长和迁移。此外,LINC00173的敲低抑制了鼻咽癌细胞在体内的肿瘤生长。这些影响可以通过下调miR-765部分逆转。GREM1是miR-765的下游靶点。敲低GREM1可抑制鼻咽癌细胞的增殖、生长和迁移。然而,这些抗肿瘤作用可以通过下调miR-765而被消除。机制上,LINC00173通过与miR-765结合增加GREM1的表达。结论:LINC00173作为一种致癌因子,通过与miR-765结合,通过上调GREM1促进鼻咽癌的进展。这项研究为NPC进展的分子机制提供了新的见解。
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Long noncoding RNA long intergenic non-protein-coding RNA 173 contributes to nasopharyngeal carcinoma progression by regulating microRNA-765/Gremlin 1 pathway.

Background: Long intergenic non-protein-coding RNA 173 (LINC00173) executes vital functions in various cancers. Nevertheless, its role and expression in nasopharyngeal carcinoma (NPC) have yet to be investigated. Here, we investigated its effects on the malignancy characteristics of NPC and elucidated the potential molecular mechanism of LINC00173 in NPC progression.

Methods: Quantitative real-time reverse transcription-PCR (qRT-PCR) and immunoblotting were conducted to estimate the LINC00173, microRNA-765 (miR-765), and Gremlin 1 (GREM1) expressions in NPC cells and tissues. Cell counting kit-8 (CCK8), colony formation, and wound healing experiments were done to evaluate the proliferation, growth, and migration of NPC cells, respectively. The tumorous growth of NPC cells in vivo was assessed through the xenograft tumor experiment. Furthermore, the interactions among miR-765, LINC00173, and GREM1 were investigated through bioinformatics analyses, luciferase reporter and RNA immunoprecipitation chip assays.

Results: An upregulated LINC00173 expression was found in NPC cell lines and tissues. The functional experiments uncovered that its downregulation repressed NPC cell proliferation, growth, and migration. In addition, LINC00173 knockdown hampered the NPC cells' tumorous growth in vivo. These effects could partially be reversed by downregulating miR-765. GREM1 is a downstream target of miR-765. GREM1 knockdown could repress the proliferation, growth, and migration of NPC cells. Nonetheless, these anti-tumor effects could be abolished by miR-765 downregulation. Mechanistically, LINC00173 increased the expression of GREM1 by binding with miR-765.

Conclusions: LINC00173 functions as an oncogenic factor by binding with miR-765 to promote the progression of NPC via GREM1 upregulation. This study provides a novel insight into the molecular mechanisms involved in NPC progression.

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来源期刊
CiteScore
5.70
自引率
3.60%
发文量
128
审稿时长
2.3 months
期刊介绍: Human and Experimental Toxicology (HET), an international peer reviewed journal, is dedicated to publishing preclinical and clinical original research papers and in-depth reviews that comprehensively cover studies of functional, biochemical and structural disorders in toxicology. The principal aim of the HET is to publish timely high impact hypothesis driven scholarly work with an international scope. The journal publishes on: Structural, functional, biochemical, and molecular effects of toxic agents; Studies that address mechanisms/modes of toxicity; Safety evaluation of novel chemical, biotechnologically-derived products, and nanomaterials for human health assessment including statistical and mechanism-based approaches; Novel methods or approaches to research on animal and human tissues (medical and veterinary patients) investigating functional, biochemical and structural disorder; in vitro techniques, particularly those supporting alternative methods
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