PTBP3 contributes to the metastasis of gastric cancer by mediating CAV1 alternative splicing

Cell Death & Disease
Xin LiangJianwen Liu

Abstract

Polypyrimidine tract-binding protein 3 (PTBP3) is an essential RNA-binding protein with roles in RNA splicing, 3' end processing and translation. Although increasing evidence implicates PTBP3 in several cancers, its role in gastric cancer metastasis remains poorly explored. In this study, we found that PTBP3 was upregulated in the gastric cancer tissues of patients with lymph node metastasis. Patients with high PTBP3 expression levels had significantly shorter survival than those with low PTBP3 expression. Overexpression/knockdown of PTBP3 expression had no effect on proliferation, whereas it regulated migration and invasion in vitro. In addition, when a mouse xenotransplant model of MKN45 was established, knockdown of PTBP3 in MKN45 cells caused the formation of tumours that were smaller in size than their counterparts, with suppression of tumour lymphangiogenesis and metastasis to regional lymph nodes. Furthermore, we identified caveolin 1 (CAV1) as a downstream target of PTBP3. RNA immunoprecipitation (RIP) assays and dual-luciferase reporter gene assays indicated that PTBP3 interacted with the CU-rich region of the CAV1 gene to downregulate CAV1α expression. Knockdown of CAV1α abrogated the reduction of FAK and Src induced ...Continue Reading

References

Sep 1, 1993·Journal of the National Cancer Institute·A M WärriP L Härkönen
Apr 17, 1999·Molecular and Cellular Biology·H YamamotoH Okayama
Jun 17, 2000·Recent Results in Cancer Research. Fortschritte Der Krebsforschung. Progrès Dans Les Recherches Sur Le Cancer·J P Sleeman
Feb 15, 2001·Nature Medicine·S A StackerM G Achen
Jul 12, 2002·Nature·Tom Maniatis, Bosiljka Tasic
May 4, 2004·Molecular and Cellular Biology·Pedro Castelo-BrancoNick Proudfoot
Jun 15, 2004·Current Opinion in Structural Biology·Liana F LareauSteven E Brenner
May 27, 2005·Biochemical Society Transactions·R SpellmanC W J Smith
Jun 16, 2005·Nature Reviews. Molecular Cell Biology·Arianne J MatlinChristopher W J Smith
Jun 28, 2005·Biochemical and Biophysical Research Communications·Feng QianQiang Xu
Dec 26, 2006·Journal of Theoretical Biology·Anna Q CaiBarry D Hughes
Mar 12, 2008·The Journal of Biological Chemistry·Kelly M Bailey, Jun Liu
Aug 28, 2010·The Biochemical Journal·Siew Ping HanRoss Smith
Mar 23, 2011·PloS One·Jakob SuckaleMichele Solimena
May 12, 2012·FEBS Letters·T F BrazãoF G Grosveld
Aug 18, 2012·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yang SongShujuan Shao
Sep 4, 2012·Mutation Research·Nina KramerHelmut Dolznig
Dec 4, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Wei LiuXu Lin
Jun 4, 2016·Oncotarget·Raquel C MontenegroSusanne Müller

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Citations

Jan 29, 2020·Journal of Cellular and Molecular Medicine·Jun MaMingyi Shang
Jul 12, 2019·Journal of Experimental & Clinical Cancer Research : CR·Pingfu HouJin Bai
Jan 4, 2020·Oncology Letters·Jiangang SunYongshun Gao
May 10, 2020·Molecular Cancer·Yiran LiangQifeng Yang
Jul 13, 2020·Journal of Hematology & Oncology·Hai QinLufeng Zheng
Feb 25, 2021·Signal Transduction and Targeted Therapy·Yuanjiao ZhangYe Yang

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Datasets Mentioned

BETA
GSE57303

Methods Mentioned

BETA
reverse transcription-PCR
transfection
immunoprecipitation
PCR
Assay

Software Mentioned

inForm
GSEA

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