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长链非编码 RNA LINC01559 通过作为 miR-1343-3p 的竞争性内源性 RNA 而上调 RAF1 表达,促进胰腺癌进展。

Long noncoding RNA LINC01559 promotes pancreatic cancer progression by acting as a competing endogenous RNA of miR-1343-3p to upregulate RAF1 expression.

机构信息

Department of Osteology, The First Peoples Hospital of Neijiang, Neijiang, Sichuan, China.

Department of Hepatic-Biliary-Pancreatic Surgery, The First Peoples Hospital of Neijiang, Neijiang, Sichuan, China.

出版信息

Aging (Albany NY). 2020 Jul 17;12(14):14452-14466. doi: 10.18632/aging.103487.

Abstract

BACKGROUND

An increasing number of studies have shown that lncRNAs are involved in the biological processes of pancreatic cancer (PC). Hence, we investigated the role of a novel noncoding RNA, LINC01559, involved in PC progression.

RESULTS

LINC01559 and RAF1 were highly expressed in PC, while miR-1343-3p had low expression. High expression of LINC01559 was significantly associated with large tumors, lymph node metastasis, and poor prognosis. Functional experiment results revealed that silencing of LINC01559 significantly suppressed PC cell proliferation and metastasis. Meanwhile, LINC01559 could act as a ceRNA to competitively sponge miR-1343-3p to up-regulate RAF1 and activate its downstream ERK pathwayConclusions: LINC01559 functions as an oncogene in PC progression through acting as a ceRNA of miR-1343-3p. Hence, LINC01559 is a potential diagnostic and therapeutic target.

METHODS

RT-qPCR was performed to determine the expression of LINC01559 and miR-1343-3p in PC. Individual patient data were collected to investigate the correlation between clinicopathological features and LINC01559 expression. Subsequently, the expression of LINC01559, miR-1343-3p, and RAF1 was altered using transfection of vectors or inhibitors. Gain- and loss-of-function assays and mechanistic assays were applied to verify the effects of LINC01559, miR-1343-3p, and RAF1 on PC cell proliferation and metastasis and

摘要

背景

越来越多的研究表明,lncRNAs 参与了胰腺癌(PC)的生物学过程。因此,我们研究了一种新型非编码 RNA,LINC01559,在 PC 进展中的作用。

结果

LINC01559 和 RAF1 在 PC 中高表达,而 miR-1343-3p 表达水平较低。LINC01559 的高表达与肿瘤体积大、淋巴结转移和预后不良显著相关。功能实验结果表明,沉默 LINC01559 可显著抑制 PC 细胞的增殖和转移。同时,LINC01559 可以作为 ceRNA 竞争性地吸附 miR-1343-3p,从而上调 RAF1 并激活其下游 ERK 通路。

结论

LINC01559 通过作为 miR-1343-3p 的 ceRNA 在 PC 进展中发挥癌基因作用。因此,LINC01559 是一个有潜在诊断和治疗价值的靶点。

方法

采用 RT-qPCR 检测 PC 中 LINC01559 和 miR-1343-3p 的表达。收集个体患者数据,探讨临床病理特征与 LINC01559 表达的相关性。随后,通过转染载体或抑制剂改变 LINC01559、miR-1343-3p 和 RAF1 的表达。通过增益和缺失功能实验以及机制实验,验证 LINC01559、miR-1343-3p 和 RAF1 对 PC 细胞增殖和转移的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abe0/7425501/fcf841f4e015/aging-12-103487-g001.jpg

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