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长链非编码RNA IUR上调miR-34a以抑制胰腺腺癌细胞的迁移和侵袭能力。

lncRNA IUR upregulates miR-34a to inhibit pancreatic adenocarcinoma cell migratory and invasive abilities.

作者信息

Li Ren, Zhang Jian, Ma Shiyang, Zhao Gang, Li Jun, Li Jiangwei, Wang Xiaoyi, Hui Bo

机构信息

Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.

Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.

出版信息

Oncol Lett. 2021 Jul;22(1):567. doi: 10.3892/ol.2021.12828. Epub 2021 May 29.

Abstract

The long non-coding RNA (lncRNA) imatinib-upregulated (IUR) has been recently reported as a tumor suppressor in leukemia. Preliminary microarray data revealed a downregulation of IUR in pancreatic adenocarcinoma (PAAD) and a positive correlation with microRNA-34a (miR-34a) expression. The present study aimed to investigate the role of IUR in PAAD. This study included samples from 58 patients with PAAD and the PAAD cell lines Capan-2 and HPAC. Reverse transcription quantitative PCR was performed to determine gene expression levels. Cell transfections were carried out to assess gene interactions between IUR, miR-34a and CD44. Transwell assays were performed to explore the effects of transfections on cell invasive and migratory abilities. The results demonstrated that IUR was downregulated in PAAD tissue compared with adjacent non-tumor tissue samples and that low expression levels of IUR correlated with poor survival in patients with PAAD. In PAAD tissue samples, the expression of IUR positively correlated with miR-34a expression but negatively correlated with CD44 expression, which is a target of miR-34a. In PAAD cells, overexpression of IUR resulted in miR-34a upregulation and CD44 downregulation. miR-34a overexpression did not affect the expression of IUR but downregulated CD44. In PAAD cells, overexpression of IUR and miR-34a led to decreased invasive and migratory abilities. However, CD44 overexpression played an opposite role and attenuated the effects of IUR and miR-34a overexpression. In conclusion, the results from this study demonstrated that IUR may upregulate miR-34a expression in order to inhibit PAAD cell migration and invasion by downregulating CD44.

摘要

长链非编码RNA(lncRNA)伊马替尼上调因子(IUR)最近被报道为白血病中的一种肿瘤抑制因子。初步的微阵列数据显示,IUR在胰腺腺癌(PAAD)中表达下调,且与微小RNA-34a(miR-34a)表达呈正相关。本研究旨在探讨IUR在PAAD中的作用。本研究纳入了58例PAAD患者的样本以及PAAD细胞系Capan-2和HPAC。采用逆转录定量PCR来测定基因表达水平。进行细胞转染以评估IUR、miR-34a和CD44之间的基因相互作用。进行Transwell实验以探究转染对细胞侵袭和迁移能力的影响。结果表明,与相邻的非肿瘤组织样本相比,IUR在PAAD组织中表达下调,且IUR低表达与PAAD患者的不良生存相关。在PAAD组织样本中,IUR的表达与miR-34a表达呈正相关,但与miR-34a的靶标CD44表达呈负相关。在PAAD细胞中,IUR的过表达导致miR-34a上调和CD44下调。miR-34a过表达不影响IUR的表达,但下调了CD44。在PAAD细胞中,IUR和miR-34a的过表达导致侵袭和迁移能力下降。然而,CD44过表达起到相反的作用,并减弱了IUR和miR-34a过表达的影响。总之,本研究结果表明,IUR可能上调miR-34a的表达,从而通过下调CD44来抑制PAAD细胞的迁移和侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5328/8185698/d1e29d81bd34/ol-22-01-12828-g00.jpg

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