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长非编码 RNA PCED1B 反义 RNA 1 通过调节 microRNA-215-3p/C-X-C 基序趋化因子受体 1 轴促进胃癌进展。

Long non-coding RNA PCED1B antisense RNA 1 promotes gastric cancer progression via modulating microRNA-215-3p / C-X-C motif chemokine receptor 1 axis.

机构信息

Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.

出版信息

Bioengineered. 2021 Dec;12(1):6083-6095. doi: 10.1080/21655979.2021.1971503.

Abstract

Long non-coding RNAs (lncRNAs) emerge as vital modulators and tissue-specific biomarkers of multiple cancers, including gastric cancer (GC). Instead, the expression characteristics, biological function and molecular mechanism of lncRNA PCED1B antisense RNA 1 (PCED1B-AS1) in GC await more elaboration. In this study, 48 cases of GC tissues and matched non-cancerous tissues were collected, and PCED1B-AS1, microRNA-215-3p (miR-215-3p) and C-X-C motif chemokine receptor 1 (CXCR1) expression levels were detected by qRT-PCR. Besides, CCK-8, EdU, Transwell and Western blot assays were conducted to assess the impact of PCED1B-AS1 or miR-215-3p on cell growth, migration, invasion and epithelial-mesenchymal transition (EMT). The interaction between genes was verified by bioinformatics analysis, rna immunoprecitipation (RIP) and dual-luciferase reporter gene assays. We demonstrated that, PCED1B-AS1 expression level was raised in GC tissues and cell lines, and increased expression of PCED1B-AS1 was in association with tumor size, TNM stage and lymph node metastasis in GC patients. Additionally, PCED1B-AS1 overexpression promoted GC cells proliferation, migration, invasion and EMT, and miR-215-3p overexpression counteracted the biological effects of PCED1B-AS1. Mechanistically, PCED1B-AS1 specifically inhibited miR-215-3p expressions, thus up-regulating CXCR1 expressions. In conclusion, PCED1B-AS1 accelerates GC progression via adsorbing miR-215-3p and up-regulating CXCR1, indicating that PCED1B-AS1 is a novel therapeutic target for treating GC.

摘要

长链非编码 RNA(lncRNA)作为多种癌症(包括胃癌(GC))的重要调节因子和组织特异性生物标志物而出现。然而,lncRNA PCED1B 反义 RNA 1(PCED1B-AS1)在 GC 中的表达特征、生物学功能和分子机制仍有待进一步阐述。在本研究中,收集了 48 例 GC 组织和配对的非癌组织,通过 qRT-PCR 检测 PCED1B-AS1、microRNA-215-3p(miR-215-3p)和 C-X-C 基序趋化因子受体 1(CXCR1)的表达水平。此外,通过 CCK-8、EdU、Transwell 和 Western blot 测定评估 PCED1B-AS1 或 miR-215-3p 对细胞生长、迁移、侵袭和上皮-间充质转化(EMT)的影响。通过生物信息学分析、rna 免疫沉淀(RIP)和双荧光素酶报告基因测定验证基因之间的相互作用。我们表明,PCED1B-AS1 在 GC 组织和细胞系中的表达水平升高,并且在 GC 患者中,PCED1B-AS1 的高表达与肿瘤大小、TNM 分期和淋巴结转移有关。此外,PCED1B-AS1 的过表达促进了 GC 细胞的增殖、迁移、侵袭和 EMT,而过表达 miR-215-3p 则抵消了 PCED1B-AS1 的生物学效应。从机制上讲,PCED1B-AS1 特异性抑制 miR-215-3p 的表达,从而上调 CXCR1 的表达。总之,PCED1B-AS1 通过吸附 miR-215-3p 并上调 CXCR1 来加速 GC 的进展,表明 PCED1B-AS1 是治疗 GC 的新治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17d8/8806612/0092cd630b96/KBIE_A_1971503_F0001_OC.jpg

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