A Novel Long Noncoding RNA HOXC-AS3 Mediates Tumorigenesis of Gastric Cancer by Binding to YBX1

Overview

Journal Genome Biol

Specialties Biology
Genetics

Date 2018 Oct 6

PMID 30286788

Citations 165

Authors

Erbao Zhang

Xuezhi He

Chongguo Zhang

Jun Su

Xiyi Lu

Xinxin Si

Jinfei Chen

Dandan Yin

Liang Han

Wei De

Affiliations

Soon will be listed here.

Abstract

Background: Recently, increasing evidence shows that long noncoding RNAs (lncRNAs) play a significant role in human tumorigenesis. However, the function of lncRNAs in human gastric cancer remains largely unknown.

Results: By using publicly available expression profiling data from gastric cancer and integrating bioinformatics analyses, we screen and identify a novel lncRNA, HOXC-AS3. HOXC-AS3 is significantly increased in gastric cancer tissues and is correlated with clinical outcomes of gastric cancer. In addition, HOXC-AS3 regulates cell proliferation and migration both in vitro and in vivo. RNA-seq analysis reveals that HOXC-AS3 knockdown preferentially affects genes that are linked to proliferation and migration. Mechanistically, we find that HOXC-AS3 is obviously activated by gain of H3K4me3 and H3K27ac, both in cells and in tissues. RNA pull-down mass spectrometry analysis identifies that YBX1 interacts with HOXC-AS3, and RNA-seq analysis finds a marked overlap in genes differentially expressed after YBX1 knockdown and those transcriptionally regulated by HOXC-AS3, suggesting that YBX1 participates in HOXC-AS3-mediated gene transcriptional regulation in the tumorigenesis of gastric cancer.

Conclusions: Together, our data demonstrate that abnormal histone modification-activated HOXC-AS3 may play important roles in gastric cancer oncogenesis and may serve as a target for gastric cancer diagnosis and therapy.

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References

Cao C, Vasilatos S, Bhargava R, Fine J, Oesterreich S, Davidson N . Functional interaction of histone deacetylase 5 (HDAC5) and lysine-specific demethylase 1 (LSD1) promotes breast cancer progression. Oncogene. 2016; 36(1):133-145. PMC: 5121103. DOI: 10.1038/onc.2016.186. View

Mo D, Fang H, Niu K, Liu J, Wu M, Li S . Human Helicase RECQL4 Drives Cisplatin Resistance in Gastric Cancer by Activating an AKT-YB1-MDR1 Signaling Pathway. Cancer Res. 2016; 76(10):3057-66. DOI: 10.1158/0008-5472.CAN-15-2361. View

Botti G, Marra L, Malzone M, Anniciello A, Botti C, Franco R . LncRNA HOTAIR as Prognostic Circulating Marker and Potential Therapeutic Target in Patients with Tumor Diseases. Curr Drug Targets. 2015; 18(1):27-34. DOI: 10.2174/1389450117666151209122950. View

Jurchott K, Kuban R, Krech T, Bluthgen N, Stein U, Walther W . Identification of Y-box binding protein 1 as a core regulator of MEK/ERK pathway-dependent gene signatures in colorectal cancer cells. PLoS Genet. 2010; 6(12):e1001231. PMC: 2996331. DOI: 10.1371/journal.pgen.1001231. View

Feng G, Dong L, Shang W, Pang X, Li J, Liu L . HDAC5 promotes cell proliferation in human hepatocellular carcinoma by up-regulating Six1 expression. Eur Rev Med Pharmacol Sci. 2014; 18(6):811-6. View

Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, Chinappi M . A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell. 2011; 147(2):358-69. PMC: 3234495. DOI: 10.1016/j.cell.2011.09.028. View

Zhou Y, Zhang X, Klibanski A . MEG3 noncoding RNA: a tumor suppressor. J Mol Endocrinol. 2012; 48(3):R45-53. PMC: 3738193. DOI: 10.1530/JME-12-0008. View

Stypula-Cyrus Y, Damania D, Kunte D, Dela Cruz M, Subramanian H, Roy H . HDAC up-regulation in early colon field carcinogenesis is involved in cell tumorigenicity through regulation of chromatin structure. PLoS One. 2013; 8(5):e64600. PMC: 3665824. DOI: 10.1371/journal.pone.0064600. View

Chen Z, Li J, Lin S, Cao C, Gimbrone N, Yang R . cAMP/CREB-regulated LINC00473 marks LKB1-inactivated lung cancer and mediates tumor growth. J Clin Invest. 2016; 126(6):2267-79. PMC: 4887185. DOI: 10.1172/JCI85250. View

10.

Zhang E, Han L, Yin D, He X, Hong L, Si X . H3K27 acetylation activated-long non-coding RNA CCAT1 affects cell proliferation and migration by regulating SPRY4 and HOXB13 expression in esophageal squamous cell carcinoma. Nucleic Acids Res. 2016; 45(6):3086-3101. PMC: 5389582. DOI: 10.1093/nar/gkw1247. View

11.

Nagano T, Fraser P . No-nonsense functions for long noncoding RNAs. Cell. 2011; 145(2):178-81. DOI: 10.1016/j.cell.2011.03.014. View

12.

Guttman M, Amit I, Garber M, French C, Lin M, Feldser D . Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 2009; 458(7235):223-7. PMC: 2754849. DOI: 10.1038/nature07672. View

13.

Lee K, Choi E, Kim M, Kim K, Jang B, Kim S . Inhibition of histone deacetylase activity down-regulates urokinase plasminogen activator and matrix metalloproteinase-9 expression in gastric cancer. Mol Cell Biochem. 2010; 343(1-2):163-71. DOI: 10.1007/s11010-010-0510-x. View

14.

Siegel R, Naishadham D, Jemal A . Cancer statistics, 2013. CA Cancer J Clin. 2013; 63(1):11-30. DOI: 10.3322/caac.21166. View

15.

Prensner J, Chinnaiyan A . The emergence of lncRNAs in cancer biology. Cancer Discov. 2011; 1(5):391-407. PMC: 3215093. DOI: 10.1158/2159-8290.CD-11-0209. View

16.

Minucci S, Pelicci P . Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer. 2006; 6(1):38-51. DOI: 10.1038/nrc1779. View

17.

Goodarzi H, Liu X, Nguyen H, Zhang S, Fish L, Tavazoie S . Endogenous tRNA-Derived Fragments Suppress Breast Cancer Progression via YBX1 Displacement. Cell. 2015; 161(4):790-802. PMC: 4457382. DOI: 10.1016/j.cell.2015.02.053. View

18.

di Pietro M, Lao-Sirieix P, Boyle S, Cassidy A, Castillo D, Saadi A . Evidence for a functional role of epigenetically regulated midcluster HOXB genes in the development of Barrett esophagus. Proc Natl Acad Sci U S A. 2012; 109(23):9077-82. PMC: 3384195. DOI: 10.1073/pnas.1116933109. View

19.

Falkenberg K, Johnstone R . Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat Rev Drug Discov. 2014; 13(9):673-91. DOI: 10.1038/nrd4360. View

20.

Catalano V, Labianca R, Beretta G, Gatta G, De Braud F, Van Cutsem E . Gastric cancer. Crit Rev Oncol Hematol. 2009; 71(2):127-64. DOI: 10.1016/j.critrevonc.2009.01.004. View