The Human RNA Surveillance Factor UPF1 ...

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Nov 28, 2017 - UPF1, UPF2 and UPF3 make up the NMD. Fig. 6. Overexpression of. UPF1 enhances chemothera- peutical sensitivity in gastric cancer cells.
Physiol Biochem 2017;42:2194-2206 Cellular Physiology Cell © 2017 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000479994 DOI: 10.1159/000479994 © 2017 The Author(s) online:August August 2017 www.karger.com/cpb Published online: 15,15, 2017 Published by S. Karger AG, Basel and Biochemistry Published www.karger.com/cpb

2194

Li et al.: UPF1 Inhibits Gastric Cancer Progression Accepted: May 21, 2017

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Original Paper

The Human RNA Surveillance Factor UPF1 Modulates Gastric Cancer Progression by Targeting Long Non-Coding RNA MALAT1 Li Lia Yingying Genga Ru Fenga4LQTLQ=KXa Bei Miaoa-LDQJ&DRb Sujuan Feia Department of Gastroenterology, b'HSDUWPHQWRI+HPDWRORJ\WKH$IÀOLDWHG+RVSLWDORI;X]KRX 0HGLFDO8QLYHUVLW\;X]KRX&KLQD

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Key Words Gastric cancer • UPF1 • MALAT1 • Hypermethylation • Nonsense-mediated mRNA decay Abstract Background/Aims: The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is overexpressed in numerous cancers. However, whether MALAT1 is regulated and the related mechanisms in gastric cancer remain unclear. Methods: ,PPXQRKLVWRFKHPLVWU\ DQG T573&5 DQDO\VHV ZHUH XVHG WR GHWHFW WKH H[SUHVVLRQ OHYHOV RI UPF1 and MALAT1 in gastric cancer and adjacent normal tissues. MTT, cell cycle, apoptosis and transwell assays were performed to examine the effects of UPF1 on cell cycle progression, FHOOSUROLIHUDWLRQDSRSWRVLVPLJUDWLRQDQGLQYDVLRQ$GGLWLRQDOO\VRGLXPELVXOIDWHVHTXHQFLQJ was used to test the promoter hypermethylation on UPF1 in gastric tumor tissues. Finally, RNA immunoprecipitation and luciferase reporter analyses demonstrated that UPF1 directly bound with MALAT1. Results: 7KH H[SUHVVLRQ RI 83) ZDV VLJQLÀFDQWO\ GRZQUHJXODWHG LQ JDVWULF cancer and negatively correlated with MALAT1 expression. Patients with lower expression of UPF1 had poorer prognosis than those with higher expression. Overexpression of UPF1 inhibited cell proliferation, cell cycle progression, cell migration and invasion, and promoted cell apoptosis in gastric cancer cells. Moreover, the UPF1-mediated inhibition of gastric cancer progression was reversed by overexpression of MALAT1. A profound downregulation of UPF1 in gastric tumor tissues was due to promoter hypermethylation. Overexpression of UPF1 LQFUHDVHGQRQVHQVHPHGLDWHGP51$GHFD\ 10' HIÀFLHQF\DQGWKXVOHGWRGRZQUHJXODWLRQ of MALAT1. Conclusion: Our results demonstrate that UPF1 is a potential modulator of MALAT1 and that UPF1/MALAT1 pathway could be a therapeutic target for gastric cancer. © 2017 The Author(s) Published by S. Karger AG, Basel

Introduction

Gastric cancer is the second leading cause of cancer worldwide [1]. Although the recent advances are acquired in gastric cancer treatment, majority of patients remain incurable

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