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Published in: Molecular Cancer 1/2018

Open Access 01-12-2018 | Research

LncRNA MT1JP functions as a ceRNA in regulating FBXW7 through competitively binding to miR-92a-3p in gastric cancer

Authors: Gang Zhang, Shuwei Li, Jiafei Lu, Yuqiu Ge, Qiaoyan Wang, Gaoxiang Ma, Qinghong Zhao, Dongdong Wu, Weida Gong, Mulong Du, Haiyan Chu, Meilin Wang, Aihua Zhang, Zhengdong Zhang

Published in: Molecular Cancer | Issue 1/2018

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Abstract

Background

Emerging evidence has shown that dysregulation function of long non-coding RNAs (lncRNAs) implicated in gastric cancer (GC). However, the role of the differentially expressed lncRNAs in GC has not fully explained.

Methods

LncRNA expression profiles were determined by lncRNA microarray in five pairs of normal and GC tissues, further validated in another 75 paired tissues by quantitative real-time PCR (qRT-PCR). Overexpression of lncRNA MT1JP was conducted to assess the effect of MT1JP in vitro and in vivo. The biological functions were demonstrated by luciferase reporter assay, western blotting and rescue experiments.

Results

LncRNA MT1JP was significantly lower in GC tissues than adjacent normal tissues, and higher MT1JP was remarkably related to lymph node metastasis and advance stage. Besides, GC patients with higher MT1JP expression had a well survival. Functionally, overexpression of lncRNA MT1JP inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro, and inhibited tumor growth and metastasis in vivo. Functional analysis showed that lncRNA MT1JP regulated FBXW7 expression by competitively binding to miR-92a-3p. MiR-92a-3p and down-regulated FBXW7 reversed cell phenotypes caused by lncRNA MT1JP by rescue analysis.

Conclusion

MT1JP, a down-regulated lncRNA in GC, was associated with malignant tumor phenotypes and survival of GC. MT1JP regulated the progression of GC by functioning as a competing endogenous RNA (ceRNA) to competitively bind to miR-92a-3p and regulate FBXW7 expression. Our study provided new insight into the post-transcriptional regulation mechanism of lncRNA MT1JP, and suggested that MT1JP may act as a potential therapeutic target and prognosis biomarker for GC.
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Literature
5.
go back to reference Khalil AM, et al. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A. 2009;106:11667–72.CrossRefPubMedPubMedCentral Khalil AM, et al. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A. 2009;106:11667–72.CrossRefPubMedPubMedCentral
7.
8.
go back to reference Thomson DW, Dinger ME. Endogenous microRNA sponges: evidence and controversy. Nat Rev Genet. 2016;17:272–83.CrossRefPubMed Thomson DW, Dinger ME. Endogenous microRNA sponges: evidence and controversy. Nat Rev Genet. 2016;17:272–83.CrossRefPubMed
10.
go back to reference Lu MH, et al. Long noncoding RNA BC032469, a novel competing endogenous RNA, upregulates hTERT expression by sponging miR-1207-5p and promotes proliferation in gastric cancer. Oncogene. 2016;35:3524–34.CrossRefPubMed Lu MH, et al. Long noncoding RNA BC032469, a novel competing endogenous RNA, upregulates hTERT expression by sponging miR-1207-5p and promotes proliferation in gastric cancer. Oncogene. 2016;35:3524–34.CrossRefPubMed
11.
go back to reference Ferlay J, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.CrossRefPubMed Ferlay J, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.CrossRefPubMed
12.
go back to reference Soerjomataram I, et al. Global burden of cancer in 2008: a systematic analysis of disability-adjusted life-years in 12 world regions. Lancet. 2012;380:1840–50.CrossRefPubMed Soerjomataram I, et al. Global burden of cancer in 2008: a systematic analysis of disability-adjusted life-years in 12 world regions. Lancet. 2012;380:1840–50.CrossRefPubMed
13.
go back to reference Liang H, Kim YH. Identifying molecular drivers of gastric cancer through next-generation sequencing. Cancer Lett. 2013;340:241–6.CrossRefPubMed Liang H, Kim YH. Identifying molecular drivers of gastric cancer through next-generation sequencing. Cancer Lett. 2013;340:241–6.CrossRefPubMed
14.
go back to reference Fang XY, Pan HF, Leng RX, Ye DQ. Long noncoding RNAs: novel insights into gastric cancer. Cancer Lett. 2015;356:357–66.CrossRefPubMed Fang XY, Pan HF, Leng RX, Ye DQ. Long noncoding RNAs: novel insights into gastric cancer. Cancer Lett. 2015;356:357–66.CrossRefPubMed
15.
go back to reference Chandra, Gupta S, Nandan Tripathi Y. Potential of long non-coding RNAs in cancer patients: from biomarkers to therapeutic targets. Int J Cancer. 2017;140(9):1955–967 Chandra, Gupta S, Nandan Tripathi Y. Potential of long non-coding RNAs in cancer patients: from biomarkers to therapeutic targets. Int J Cancer. 2017;140(9):1955–967
16.
go back to reference Xue Y, et al. Genome-wide analysis of long noncoding RNA signature in human colorectal cancer. Gene. 2015;556:227–34.CrossRefPubMed Xue Y, et al. Genome-wide analysis of long noncoding RNA signature in human colorectal cancer. Gene. 2015;556:227–34.CrossRefPubMed
18.
19.
20.
go back to reference Sun TT, et al. LncRNA GClnc1 promotes gastric carcinogenesis and may act as a modular scaffold of WDR5 and KAT2A complexes to specify the histone modification pattern. Cancer Discov. 2016;6:784–801.CrossRefPubMed Sun TT, et al. LncRNA GClnc1 promotes gastric carcinogenesis and may act as a modular scaffold of WDR5 and KAT2A complexes to specify the histone modification pattern. Cancer Discov. 2016;6:784–801.CrossRefPubMed
21.
go back to reference Liu L, et al. LncRNA MT1JP functions as a tumor suppressor by interacting with TIAR to modulate the p53 pathway. Oncotarget. 2016;7:15787–800.PubMedPubMedCentral Liu L, et al. LncRNA MT1JP functions as a tumor suppressor by interacting with TIAR to modulate the p53 pathway. Oncotarget. 2016;7:15787–800.PubMedPubMedCentral
22.
go back to reference Hu Y, Tian H, Xu J, Fang JY. Roles of competing endogenous RNAs in gastric cancer. Brief Funct Genomics. 2016;15:266–73.CrossRefPubMed Hu Y, Tian H, Xu J, Fang JY. Roles of competing endogenous RNAs in gastric cancer. Brief Funct Genomics. 2016;15:266–73.CrossRefPubMed
24.
go back to reference Liu XH, et al. Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol Cancer. 2014;13:92.CrossRefPubMedPubMedCentral Liu XH, et al. Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol Cancer. 2014;13:92.CrossRefPubMedPubMedCentral
25.
go back to reference Ren C, et al. Expression and prognostic value of miR-92a in patients with gastric cancer. Tumour Biol. 2016;37:9483–91.CrossRefPubMed Ren C, et al. Expression and prognostic value of miR-92a in patients with gastric cancer. Tumour Biol. 2016;37:9483–91.CrossRefPubMed
26.
go back to reference Wu Q, et al. MiR-19b/20a/92a regulates the self-renewal and proliferation of gastric cancer stem cells. J Cell Sci. 2013;126:4220–9.CrossRefPubMed Wu Q, et al. MiR-19b/20a/92a regulates the self-renewal and proliferation of gastric cancer stem cells. J Cell Sci. 2013;126:4220–9.CrossRefPubMed
27.
go back to reference Yang W, et al. MicroRNA-92a contributes to tumor growth of human hepatocellular carcinoma by targeting FBXW7. Oncol Rep. 2015;34:2576–84.CrossRefPubMed Yang W, et al. MicroRNA-92a contributes to tumor growth of human hepatocellular carcinoma by targeting FBXW7. Oncol Rep. 2015;34:2576–84.CrossRefPubMed
28.
go back to reference Zhou C. et al. miR-92a is upregulated in cervical cancer and promotes cell proliferation and invasion by targeting FBXW7. Biochem Biophys Res Commun. 2015;458:63–9.CrossRefPubMed Zhou C. et al. miR-92a is upregulated in cervical cancer and promotes cell proliferation and invasion by targeting FBXW7. Biochem Biophys Res Commun. 2015;458:63–9.CrossRefPubMed
29.
go back to reference Liu C, Zhang Y, Chen H, Jiang L, Xiao D. Function analysis of rs9589207 polymorphism in miR-92a in gastric cancer. Tumour Biol. 2016;37:4439–44.CrossRefPubMed Liu C, Zhang Y, Chen H, Jiang L, Xiao D. Function analysis of rs9589207 polymorphism in miR-92a in gastric cancer. Tumour Biol. 2016;37:4439–44.CrossRefPubMed
30.
go back to reference Welcker M, Clurman BE. FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation. Nat Rev Cancer. 2008;8:83–93.CrossRefPubMed Welcker M, Clurman BE. FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation. Nat Rev Cancer. 2008;8:83–93.CrossRefPubMed
31.
32.
go back to reference Akhoondi S, et al. FBXW7/hCDC4 is a general tumor suppressor in human cancer. Cancer Res. 2007;67:9006–12.CrossRefPubMed Akhoondi S, et al. FBXW7/hCDC4 is a general tumor suppressor in human cancer. Cancer Res. 2007;67:9006–12.CrossRefPubMed
33.
go back to reference Li H, et al. Fbxw7 regulates tumor apoptosis, growth arrest and the epithelial-to-mesenchymal transition in part through the RhoA signaling pathway in gastric cancer. Cancer Lett. 2016;370:39–55.CrossRefPubMed Li H, et al. Fbxw7 regulates tumor apoptosis, growth arrest and the epithelial-to-mesenchymal transition in part through the RhoA signaling pathway in gastric cancer. Cancer Lett. 2016;370:39–55.CrossRefPubMed
34.
go back to reference Eto K, et al. The sensitivity of gastric cancer to trastuzumab is regulated by the miR-223/FBXW7 pathway. Int J Cancer. 2015;136:1537–45.CrossRefPubMed Eto K, et al. The sensitivity of gastric cancer to trastuzumab is regulated by the miR-223/FBXW7 pathway. Int J Cancer. 2015;136:1537–45.CrossRefPubMed
Metadata
Title
LncRNA MT1JP functions as a ceRNA in regulating FBXW7 through competitively binding to miR-92a-3p in gastric cancer
Authors
Gang Zhang
Shuwei Li
Jiafei Lu
Yuqiu Ge
Qiaoyan Wang
Gaoxiang Ma
Qinghong Zhao
Dongdong Wu
Weida Gong
Mulong Du
Haiyan Chu
Meilin Wang
Aihua Zhang
Zhengdong Zhang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2018
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-018-0829-6

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