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Published in: Clinical and Translational Oncology 10/2020

01-10-2020 | Esophageal Cancer | Research Article

Long noncoding RNA SNHG12 suppresses esophageal squamous cell carcinoma progression through competing endogenous RNA networks

Authors: M. Liang, Z. Pan, F. Yu, C. Chen

Published in: Clinical and Translational Oncology | Issue 10/2020

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Abstract

Purpose

Esophageal squamous cell cancer (ESCC) has high rates of recurrence and mortality. Small nucleolar RNA host gene 12 (SNHG12) is known to promote the progression of several cancers. Therefore, we aimed to investigate the expression and role of SNHG12 in ESCC.

Methods

The expression and clinical value of SNHG12 in esophageal cancer were explored using data from The Cancer Genome Atlas (TCGA) and the online server GEPIA. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to verify the expression levels of SNHG12 in ESCC tissues and cell lines. Furthermore, loss-of-function assays were performed to examine the effect of SNHG12 on ESCC cells in vitro and in vivo. The potential competing endogenous RNA networks of SNHG12 in ESCC were explored.

Results

SNHG12 was downregulated in human ESCA tissues compared to control tissues. The expression of SNHG12 was strongly associated with T stage, N stage, and TNM stage. Low SNHG12 expression in esophageal tumor tissues was significantly correlated with poor prognosis. Furthermore, knockdown of SNHG12 not only promoted proliferation, colony formation, migration, and invasion and inhibited apoptosis in ESCC cells in vitro, but also increased tumor growth in vivo. Additionally, this proves that the SNHG12/miRNA-195-5p/BCL9 network might be involved in ESCC.

Conclusion

This is the first study to reveal that SNHG12 is downregulated in ESCC tissues and could be used as a prognostic tool. SNHG12 suppressed tumor progression in ESCC cells, serving as a potential biomarker. The SNHG12/miRNA-195-5p/BCL9 network is proposed to be the mechanism leading to ESCC progression.
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Literature
1.
go back to reference Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.PubMedCrossRef Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.PubMedCrossRef
2.
go back to reference Chen W, Zheng R, Zeng H, Zhang S. The updated incidences and mortalities of major cancers in China, 2011. Chin J cancer. 2015;34(11):502–7.PubMed Chen W, Zheng R, Zeng H, Zhang S. The updated incidences and mortalities of major cancers in China, 2011. Chin J cancer. 2015;34(11):502–7.PubMed
3.
go back to reference Ohashi S, Miyamoto S, Kikuchi O, Goto T, Amanuma Y, Muto M. Recent advances from basic and clinical studies of esophageal squamous cell carcinoma. Gastroenterology. 2015;149(7):1700–15.PubMedCrossRef Ohashi S, Miyamoto S, Kikuchi O, Goto T, Amanuma Y, Muto M. Recent advances from basic and clinical studies of esophageal squamous cell carcinoma. Gastroenterology. 2015;149(7):1700–15.PubMedCrossRef
4.
go back to reference Straatman J, Joosten PJ, Terwee CB, Cuesta MA, Jansma EP, van der Peet DL. Systematic review of patient-reported outcome measures in the surgical treatment of patients with esophageal cancer. Dis Esophagus. 2016;29(7):760–72.PubMedCrossRef Straatman J, Joosten PJ, Terwee CB, Cuesta MA, Jansma EP, van der Peet DL. Systematic review of patient-reported outcome measures in the surgical treatment of patients with esophageal cancer. Dis Esophagus. 2016;29(7):760–72.PubMedCrossRef
5.
go back to reference Ding S, Qu W, Jiao Y, Zhang J, Zhang C, Dang S. LncRNA SNHG12 promotes the proliferation and metastasis of papillary thyroid carcinoma cells through regulating wnt/beta-catenin signaling pathway. Cancer biomarkers: section A of Disease markers. 2018;22(2):217–26.CrossRef Ding S, Qu W, Jiao Y, Zhang J, Zhang C, Dang S. LncRNA SNHG12 promotes the proliferation and metastasis of papillary thyroid carcinoma cells through regulating wnt/beta-catenin signaling pathway. Cancer biomarkers: section A of Disease markers. 2018;22(2):217–26.CrossRef
6.
go back to reference Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 2009;458(7235):223–7.PubMedPubMedCentralCrossRef Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 2009;458(7235):223–7.PubMedPubMedCentralCrossRef
8.
9.
go back to reference Saxena A, Carninci P. Long non-coding RNA modifies chromatin: epigenetic silencing by long non-coding RNAs. BioEssays: news and reviews in molecular, cellular and developmental biology. 2011;33(11):830–9.CrossRef Saxena A, Carninci P. Long non-coding RNA modifies chromatin: epigenetic silencing by long non-coding RNAs. BioEssays: news and reviews in molecular, cellular and developmental biology. 2011;33(11):830–9.CrossRef
11.
go back to reference Ding C, Cheng S, Yang Z, Lv Z, Xiao H, Du C, et al. Long non-coding RNA HOTAIR promotes cell migration and invasion via down-regulation of RNA binding motif protein 38 in hepatocellular carcinoma cells. Int J Mol Sci. 2014;15(3):4060–76.PubMedPubMedCentralCrossRef Ding C, Cheng S, Yang Z, Lv Z, Xiao H, Du C, et al. Long non-coding RNA HOTAIR promotes cell migration and invasion via down-regulation of RNA binding motif protein 38 in hepatocellular carcinoma cells. Int J Mol Sci. 2014;15(3):4060–76.PubMedPubMedCentralCrossRef
12.
go back to reference Tripathi V, Shen Z, Chakraborty A, Giri S, Freier SM, Wu X, et al. Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-MYB. PLoS Genet. 2013;9(3):e1003368.PubMedPubMedCentralCrossRef Tripathi V, Shen Z, Chakraborty A, Giri S, Freier SM, Wu X, et al. Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-MYB. PLoS Genet. 2013;9(3):e1003368.PubMedPubMedCentralCrossRef
13.
go back to reference Liao LM, Sun XY, Liu AW, Wu JB, Cheng XL, Lin JX, et al. Low expression of long noncoding XLOC_010588 indicates a poor prognosis and promotes proliferation through upregulation of c-Myc in cervical cancer. Gynecol Oncol. 2014;133(3):616–23.PubMedCrossRef Liao LM, Sun XY, Liu AW, Wu JB, Cheng XL, Lin JX, et al. Low expression of long noncoding XLOC_010588 indicates a poor prognosis and promotes proliferation through upregulation of c-Myc in cervical cancer. Gynecol Oncol. 2014;133(3):616–23.PubMedCrossRef
14.
go back to reference Zhai W, Li X, Wu S, Zhang Y, Pang H, Chen W. Microarray expression profile of lncRNAs and the upregulated ASLNC04080 lncRNA in human endometrial carcinoma. Int J Oncol. 2015;46(5):2125–37.PubMedCrossRef Zhai W, Li X, Wu S, Zhang Y, Pang H, Chen W. Microarray expression profile of lncRNAs and the upregulated ASLNC04080 lncRNA in human endometrial carcinoma. Int J Oncol. 2015;46(5):2125–37.PubMedCrossRef
15.
go back to reference Zhou S, Yu L, Xiong M, Dai G. LncRNA SNHG12 promotes tumorigenesis and metastasis in osteosarcoma by upregulating Notch2 by sponging miR-195-5p. Biochem Biophys Res Commun. 2018;495(2):1822–32.PubMedCrossRef Zhou S, Yu L, Xiong M, Dai G. LncRNA SNHG12 promotes tumorigenesis and metastasis in osteosarcoma by upregulating Notch2 by sponging miR-195-5p. Biochem Biophys Res Commun. 2018;495(2):1822–32.PubMedCrossRef
16.
go back to reference Ruan W, Wang P, Feng S, Xue Y, Li Y. Long non-coding RNA small nucleolar RNA host gene 12 (SNHG12) promotes cell proliferation and migration by upregulating angiomotin gene expression in human osteosarcoma cells. Tumour Biol. 2016;37(3):4065–73.PubMedCrossRef Ruan W, Wang P, Feng S, Xue Y, Li Y. Long non-coding RNA small nucleolar RNA host gene 12 (SNHG12) promotes cell proliferation and migration by upregulating angiomotin gene expression in human osteosarcoma cells. Tumour Biol. 2016;37(3):4065–73.PubMedCrossRef
17.
go back to reference Jin XJ, Chen XJ, Zhang ZF, Hu WS, Ou RY, Li S, et al. Long noncoding RNA SNHG12 promotes the progression of cervical cancer via modulating miR-125b/STAT3 axis. J Cell Physiol. 2019;234(5):6624–32.PubMedCrossRef Jin XJ, Chen XJ, Zhang ZF, Hu WS, Ou RY, Li S, et al. Long noncoding RNA SNHG12 promotes the progression of cervical cancer via modulating miR-125b/STAT3 axis. J Cell Physiol. 2019;234(5):6624–32.PubMedCrossRef
18.
go back to reference Dong J, Wang Q, Li L, Xiao-Jin Z. Upregulation of long non-coding RNA small nucleolar RNA host gene 12 contributes to cell growth and invasion in cervical cancer by acting as a sponge for MiR-424-5p. Cell Physiol Biochem. 2018;45(5):2086–94.PubMedCrossRef Dong J, Wang Q, Li L, Xiao-Jin Z. Upregulation of long non-coding RNA small nucleolar RNA host gene 12 contributes to cell growth and invasion in cervical cancer by acting as a sponge for MiR-424-5p. Cell Physiol Biochem. 2018;45(5):2086–94.PubMedCrossRef
19.
go back to reference Sun Y, Liu J, Chu L, Yang W, Liu H, Li C, et al. Long noncoding RNA SNHG12 facilitates the tumorigenesis of glioma through miR-101-3p/FOXP1 axis. Gene. 2018;676:315–21.PubMedCrossRef Sun Y, Liu J, Chu L, Yang W, Liu H, Li C, et al. Long noncoding RNA SNHG12 facilitates the tumorigenesis of glioma through miR-101-3p/FOXP1 axis. Gene. 2018;676:315–21.PubMedCrossRef
20.
go back to reference Wang JZ, Xu CL, Wu H, Shen SJ. LncRNA SNHG12 promotes cell growth and inhibits cell apoptosis in colorectal cancer cells. Braz J Med Biol Res. 2017;50(3):e6079.PubMedPubMedCentralCrossRef Wang JZ, Xu CL, Wu H, Shen SJ. LncRNA SNHG12 promotes cell growth and inhibits cell apoptosis in colorectal cancer cells. Braz J Med Biol Res. 2017;50(3):e6079.PubMedPubMedCentralCrossRef
21.
go back to reference Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98–W102.PubMedPubMedCentralCrossRef Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98–W102.PubMedPubMedCentralCrossRef
22.
go back to reference Li JH, Liu S, Zhou H, Qu LH, Yang JH. starBase v2.0. decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic acids research. 2014, 42(Database issue): D92–97. Li JH, Liu S, Zhou H, Qu LH, Yang JH. starBase v2.0. decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic acids research. 2014, 42(Database issue): D92–97.
23.
go back to reference Brown TC, Nicolson NG, Korah R, Carling T. BCL9 upregulation in adrenocortical carcinoma: a novel Wnt/β-catenin activating event driving adrenocortical malignancy. J Am Coll Surg. 2018;226(6):988–95.PubMedCrossRef Brown TC, Nicolson NG, Korah R, Carling T. BCL9 upregulation in adrenocortical carcinoma: a novel Wnt/β-catenin activating event driving adrenocortical malignancy. J Am Coll Surg. 2018;226(6):988–95.PubMedCrossRef
24.
go back to reference Guil S, Esteller M. RNA-RNA interactions in gene regulation: the coding and noncoding players. Trends Biochem Sci. 2015;40(5):248–56.PubMedCrossRef Guil S, Esteller M. RNA-RNA interactions in gene regulation: the coding and noncoding players. Trends Biochem Sci. 2015;40(5):248–56.PubMedCrossRef
25.
go back to reference Wang O, Yang F, Liu Y, Lv L, Ma R, Chen C, et al. C-MYC-induced upregulation of lncRNA SNHG12 regulates cell proliferation, apoptosis and migration in triple-negative breast cancer. Am J Transl Res. 2017;9(2):533–45.PubMedPubMedCentral Wang O, Yang F, Liu Y, Lv L, Ma R, Chen C, et al. C-MYC-induced upregulation of lncRNA SNHG12 regulates cell proliferation, apoptosis and migration in triple-negative breast cancer. Am J Transl Res. 2017;9(2):533–45.PubMedPubMedCentral
26.
go back to reference Wang X, Qi G, Zhang J, Wu J, Zhou N, Li L, et al. Knockdown of long noncoding RNA small nucleolar RNA host gene 12 inhibits cell growth and induces apoptosis by upregulating miR-138 in nonsmall cell lung cancer. DNA Cell Biol. 2017;36(11):892–900.PubMedCrossRef Wang X, Qi G, Zhang J, Wu J, Zhou N, Li L, et al. Knockdown of long noncoding RNA small nucleolar RNA host gene 12 inhibits cell growth and induces apoptosis by upregulating miR-138 in nonsmall cell lung cancer. DNA Cell Biol. 2017;36(11):892–900.PubMedCrossRef
27.
go back to reference Lan T, Ma W, Hong Z, Wu L, Chen X, Yuan Y. Long non-coding RNA small nucleolar RNA host gene 12 (SNHG12) promotes tumorigenesis and metastasis by targeting miR-199a/b-5p in hepatocellular carcinoma. J Exp Clin Cancer Res. 2017;36(1):11.PubMedPubMedCentralCrossRef Lan T, Ma W, Hong Z, Wu L, Chen X, Yuan Y. Long non-coding RNA small nucleolar RNA host gene 12 (SNHG12) promotes tumorigenesis and metastasis by targeting miR-199a/b-5p in hepatocellular carcinoma. J Exp Clin Cancer Res. 2017;36(1):11.PubMedPubMedCentralCrossRef
28.
go back to reference Zhu L, Zhang X, Fu X, Li Z, Sun Z, Wu J, et al. c-Myc mediated upregulation of long noncoding RNA SNHG12 regulates proliferation and drug sensitivity in natural killer/T-cell lymphoma. J Cell Biochem. 2019;120(8):12628–377.PubMedCrossRef Zhu L, Zhang X, Fu X, Li Z, Sun Z, Wu J, et al. c-Myc mediated upregulation of long noncoding RNA SNHG12 regulates proliferation and drug sensitivity in natural killer/T-cell lymphoma. J Cell Biochem. 2019;120(8):12628–377.PubMedCrossRef
29.
go back to reference Song J, Wu X, Ma R, Miao L, Xiong L, Zhao W. Long noncoding RNA SNHG12 promotes cell proliferation and activates Wnt/beta-catenin signaling in prostate cancer through sponging microRNA-195. J Cell Biochem. 2019;120(8):13066–75.PubMedCrossRef Song J, Wu X, Ma R, Miao L, Xiong L, Zhao W. Long noncoding RNA SNHG12 promotes cell proliferation and activates Wnt/beta-catenin signaling in prostate cancer through sponging microRNA-195. J Cell Biochem. 2019;120(8):13066–75.PubMedCrossRef
Metadata
Title
Long noncoding RNA SNHG12 suppresses esophageal squamous cell carcinoma progression through competing endogenous RNA networks
Authors
M. Liang
Z. Pan
F. Yu
C. Chen
Publication date
01-10-2020
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology / Issue 10/2020
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-020-02317-7

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