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长链非编码 RNA MNX1-AS1 通过调控 miR-744-5p/BCL9/β-连环蛋白轴促进喉鳞状细胞癌的生长和迁移。

LncRNA MNX1-AS1 Contributes to Laryngeal Squamous Cell Carcinoma Growth and Migration by Regulating mir-744-5p/bcl9/β-Catenin Axis.

机构信息

Department of Otolaryngology, the First Affiliated Hospital, Huzhou University, the First People's Hospital of Huzhou, Huzhou City, Zhejiang Province, China.

Department of Surgical Anesthesiology, the First Affiliated Hospital, Huzhou University, the First People's Hospital of Huzhou, Huzhou City, Zhejiang Province, China.

出版信息

Cell Transplant. 2021 Jan-Dec;30:9636897211005682. doi: 10.1177/09636897211005682.

Abstract

Increasing evidence has indicated that long noncoding RNAs (lncRNAs) are involved in the progression of laryngeal squamous cell carcinoma (LSCC). Here, we aimed to disclose the role of MNX1-AS1 in LSCC progression, and explore whether MNX1-AS1 participates in LSCC progression via targeting miR-744-5p to active BCL9/β-catenin signaling. Sixty-five human LSCC tissues and the paracancerous normal tissues were recruited to determine the levels of MNX1-AS1, miR-744-5p and BCL9 using qRT-PCR. The interaction of miR-744-5p and MNX1-AS1/BCL9 was determined by using the RNA immunoprecipitation (RIP) assay and/or luciferase gene reporter assay. Cell viability, tumor formation, invasion and migration abilities were detected by MTT, Xenograft models and Transwell assays. MNX1-AS1 level was increased significantly in human LSCC tissues as compared with the normal tissues, which showed a positive correlation with BCL9 level while a negative correlation with miR-744-5p level. High level of MNX1-AS1 predicted a poor prognosis and an advanced clinical process in LSCC patients. miR-744-5p targeted upregulation weakened the luciferase activity of MNX1-AS1 and /BCL9, and downregulated their expression levels-wt, while showed no effect when the binding sites were mutated. Knockdown of MNX1-AS1 markedly weakened cell viability, migration, and invasion abilities, while BCL9 overexpression abolished these tendencies. In addition, MNX1-AS1 downregulation induced decreases in tumor volumes and weights , accompanied by reductions in BCL9, Ki-67 and β-catenin expression and an increase in miR-744-5p expression. Collectively, this study reveals that MNX1-AS1 contributes to cell growth and migration by regulating miR-744-5p/BCL9/β-catenin axis in LSCC.

摘要

越来越多的证据表明,长链非编码 RNA(lncRNA)参与了喉鳞状细胞癌(LSCC)的进展。在这里,我们旨在揭示 MNX1-AS1 在 LSCC 进展中的作用,并探讨 MNX1-AS1 是否通过靶向 miR-744-5p 来激活 BCL9/β-catenin 信号通路参与 LSCC 进展。招募了 65 个人 LSCC 组织和癌旁正常组织,通过 qRT-PCR 确定 MNX1-AS1、miR-744-5p 和 BCL9 的水平。通过 RNA 免疫沉淀(RIP)测定和/或荧光素酶基因报告基因测定确定 miR-744-5p 和 MNX1-AS1/BCL9 的相互作用。通过 MTT、异种移植模型和 Transwell 测定检测细胞活力、肿瘤形成、侵袭和迁移能力。与正常组织相比,MNX1-AS1 在人 LSCC 组织中的水平显著升高,与 BCL9 水平呈正相关,与 miR-744-5p 水平呈负相关。MNX1-AS1 水平高预示 LSCC 患者预后不良,临床进程进展。miR-744-5p 的靶向上调减弱了 MNX1-AS1 和/或 BCL9 的荧光素酶活性,并下调了它们的表达水平-wt,而当结合位点发生突变时则没有影响。MNX1-AS1 的敲低显著减弱了细胞活力、迁移和侵袭能力,而 BCL9 的过表达则消除了这些趋势。此外,MNX1-AS1 的下调导致肿瘤体积和重量的减少,同时降低了 BCL9、Ki-67 和 β-catenin 的表达,增加了 miR-744-5p 的表达。总之,这项研究揭示了 MNX1-AS1 通过调节 miR-744-5p/BCL9/β-catenin 轴在 LSCC 中促进细胞生长和迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d52/8033468/b3c557aab11c/10.1177_09636897211005682-fig1.jpg

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