Current issue
Archive
Manuscripts accepted
About the Journal
Editorial office
Editorial board
Section Editors
Abstracting and indexing
Subscription
Contact
Ethical standards and procedures
Most read articles
Instructions for authors
Article Processing Charge (APC)
Regulations of paying article processing charge (APC)
GASTROENTEROLOGY / BASIC RESEARCH
TUG1 acts as a biomarker to predict the relapse of gastric cancer after endoscopic submucosal dissection
1
Department of Gastroenterology, The First People’s Hospital of Yancheng, Yancheng, Jiangsu, China
Submission date: 2019-07-30
Final revision date: 2020-01-30
Acceptance date: 2020-03-11
Online publication date: 2021-03-28
Corresponding author
Yanping Hao
Department of Gastroenterology, The First People’s Hospital of Yancheng, No.66 Renmin Road, Yancheng, Jiangsu 224005, China
Department of Gastroenterology, The First People’s Hospital of Yancheng, No.66 Renmin Road, Yancheng, Jiangsu 224005, China
Arch Med Sci 2025;21(4):1502-1512
KEYWORDS
TOPICS
ABSTRACT
Introduction:
MiR-382 was reported to act as a prognostic biomarker for the relapse of gastric cancer (GC) after endoscopic mucosal resection (EMR). In addition, TUG1 was reported to regulate cell proliferation via sponging miR-382. Therefore, in this study, we aimed to investigate the value of TUG1 in predicting post-EMR relapse of GC.
Material and methods:
The log rank test was utilized to analyze relapse-free rate and validate the prognostic value of TUG1 in predicting post-EMR GC relapse. Real-time PCR, Western blot and luciferase assays were performed to clarify the regulatory relationships among TUG1, miR-382 and CD44, thus establishing a TUG1/miR-382/CD44 signaling pathway. Moreover, MTT assays were conducted to observe the effect of TUG1 on cell proliferation and post-EMR GC relapse.
Results:
The AUC of the high TUG1 expression group was obviously smaller than that of the low TUG1 expression group, which indicated that the expression of TUG1 could be used as a prognostic biomarker to predict the risk of post-EMR GC relapse. In addition, a negative correlation was found between miR-382 expression and the expression of its endogenous competing RNA TUG1. Furthermore, miR-382 was shown to inhibit the expression of its target gene CD44. Finally, a TUG1/miR-382/CD44 signaling pathway was established and was implicated in post-EMR recurrence of GC, and the overexpression of TUG1 was shown to promote the proliferation of GC cells.
Conclusions:
Reduced expression of TUG1 could inhibit the proliferation of GC cells and increase the expression of miR-382, which in turn down-regulated CD44 expression and lowered the risk of post-EMR GC relapse.
MiR-382 was reported to act as a prognostic biomarker for the relapse of gastric cancer (GC) after endoscopic mucosal resection (EMR). In addition, TUG1 was reported to regulate cell proliferation via sponging miR-382. Therefore, in this study, we aimed to investigate the value of TUG1 in predicting post-EMR relapse of GC.
Material and methods:
The log rank test was utilized to analyze relapse-free rate and validate the prognostic value of TUG1 in predicting post-EMR GC relapse. Real-time PCR, Western blot and luciferase assays were performed to clarify the regulatory relationships among TUG1, miR-382 and CD44, thus establishing a TUG1/miR-382/CD44 signaling pathway. Moreover, MTT assays were conducted to observe the effect of TUG1 on cell proliferation and post-EMR GC relapse.
Results:
The AUC of the high TUG1 expression group was obviously smaller than that of the low TUG1 expression group, which indicated that the expression of TUG1 could be used as a prognostic biomarker to predict the risk of post-EMR GC relapse. In addition, a negative correlation was found between miR-382 expression and the expression of its endogenous competing RNA TUG1. Furthermore, miR-382 was shown to inhibit the expression of its target gene CD44. Finally, a TUG1/miR-382/CD44 signaling pathway was established and was implicated in post-EMR recurrence of GC, and the overexpression of TUG1 was shown to promote the proliferation of GC cells.
Conclusions:
Reduced expression of TUG1 could inhibit the proliferation of GC cells and increase the expression of miR-382, which in turn down-regulated CD44 expression and lowered the risk of post-EMR GC relapse.
REFERENCES (46)
1.
Kelley JR, Duggan JM. Gastric cancer epidemiology and risk factors. J Clin Epidemiol 2003; 56: 1-9.
2.
Montgomery E, Goldblum JR, Greenson JK, et al. Dysplasia as a predictive marker for invasive carcinoma in Barrett esophagus: a follow-up study based on 138 cases from a diagnostic variability study. Hum Pathol 2001; 32: 379-88.
3.
De Ceglie A, Hassan C, Mangiavillano B, et al. Endoscopic mucosal resection and endoscopic submucosal dissection for colorectal lesions: a systematic review. Crit Rev Oncol Hematol 2016; 104: 138-55.
4.
Soehendra N, Binmoeller KF, Bohnacker S, et al. Endoscopic snare mucosectomy in the esophagus without any additional equipment: a simple technique for resection of flat early cancer. Endoscopy 1997; 29: 380-3.
5.
Chang KJ, Yoshinaka R, Nguyen P. Endoscopic ultrasound-assisted band ligation: a new technique for resection of submucosal tumors. Gastrointest Endosc 1996; 44: 720-2.
6.
Ortiz AM, Bhargavi P, Zuckerman MJ, Othman MO. Endoscopic mucosal resection recurrence rate for colorectal lesions. South Med J 2014; 107: 615-21.
7.
Rajan E, Gostout CJ, Feitoza AB, et al. Widespread EMR: a new technique for removal of large areas of mucosa. Gastrointest Endosc 2004; 60: 623-7.
8.
Valerii G, Tringali A, Landi R, et al. Endoscopic mucosal resection of non-ampullary sporadic duodenal adenomas: a retrospective analysis with long-term follow-up. Scand J Gastroenterol 2018; 53: 490-4.
9.
Uno K, Koike T, Kusaka G, Takahashi Y, Ara N, Shimosegawa T. Risk of metachronous recurrence after endoscopic submucosal dissection of esophageal squamous cell carcinoma. Dis Esophagus 2017; 30: 1-8.
10.
Tao M, Zhou X, Hu M, Pan J. Endoscopic submucosal dissection versus endoscopic mucosal resection for patients with early gastric cancer: a meta-analysis. BMJ Open 2019; 9: e025803.
11.
Chaber-Ciopinska A, Kiprian D, Kawecki A, Kaminski MF. Surveillance of patients at high-risk of squamous cell esophageal cancer. Best Pract Res Clin Gastroenterol 2016; 30: 893-900.
12.
International Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature 2004; 431: 931-45.
13.
Wilusz JE, Sunwoo H, Spector DL. Long noncoding RNAs: functional surprises from the RNA world. Genes Dev 2009; 23: 1494-504.
14.
Chen Z, Gao Y, Gao S, Song D, Feng Y. MiR-135b-5p promotes viability, proliferation, migration and invasion of gastric cancer cells by targeting Krüppel-like factor 4 (KLF4). Arch Med Sci 2020; 16: 167-76.
15.
Liu X, Wang M, Cui Y. LncRNA TP73-AS1 interacted with miR-141-3p to promote the proliferation of non-small cell lung cancer. Arch Med Sci 2019; 15: 1547-54.
16.
Young TL, Matsuda T, Cepko CL. The noncoding RNA taurine upregulated gene 1 is required for differentiation of the murine retina. Curr Biol 2005; 15: 501-12.
17.
Khalil AM, Guttman M, Huarte M, et al. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci USA 2009; 106: 11667-72.
18.
Zhao L, Sun H, Kong H, Chen Z, Chen B, Zhou M. LncRNA-TUG1/EZH2 axis promotes cell proliferation, migration and the EMT phenotype formation through sponging miR-382. Cell Physiol Biochem 2017; 42: 2145-58.
19.
Ponta H, Sherman L, Herrlich PA. CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol 2003; 4: 33-45.
20.
Kallakury BV, Yang F, Figge J, et al. Decreased levels of CD44 protein and mRNA in prostate carcinoma. Correlation with tumor grade and ploidy. Cancer 1996; 78: 1461-9.
21.
Liang G, Li S, Du W, Ke Q, Cai J, Yang J. Hypoxia regulates CD44 expression via hypoxia-inducible factor-1alpha in human gastric cancer cells. Oncol Lett 2017; 13: 967-72.
22.
Li JY, Liu CP, Shiao WC, et al. Inhibitory effect of PDGF-BB and serum-stimulated responses in vascular smooth muscle cell proliferation by hinokitiol via up-regulation of p21 and p53. Arch Med Sci 2018; 14: 579-87.
23.
Xue HG, Yang AH, Sun XG, Lu YY, Tian ZB. Expression of microRNA-328 functions as a biomarker for recurrence of early gastric cancer (EGC) after endoscopic submucosal dissection (ESD) by modulating CD44. Med Sci Monit 2016; 22: 4779-85.
24.
Zhao L, Sun H, Kong H, Chen Z, Chen B, Zhou M. The LncRNA-TUG1/EZH2 axis promotes pancreatic cancer cell proliferation, migration and EMT phenotype formation through sponging mir-382. Cell Physiol Biochem 2017; 42: 2145-58.
25.
Chiu PW. Novel endoscopic therapeutics for early gastric cancer. Clin Gastroenterowl Hepatol 2014; 12: 120-5.
26.
Ono H, Kondo H, Gotoda T, et al. Endoscopic mucosal resection for treatment of early gastric cancer. Gut 2001; 48: 225-9.
27.
Kojima T, Parra-Blanco A, Takahashi H, Fujita R. Outcome of endoscopic mucosal resection for early gastric cancer: review of the Japanese literature. Gastrointest Endosc 1998; 48: 550-4; discussion 554-5.
28.
Ji TT, Xuan H, Jie J, et al. Inhibition of long non-coding RNA TUG1 on gastric cancer cell transference and invasion through regulating and controlling the expression of miR-144/c-Met axis. Asian Pac J Trop Med 2016; 9: 508-12.
29.
Zhang Q, Geng PL, Yin P, Wang XL, Jia JP, Yao J. Down-regulation of long non-coding RNA TUG1 inhibits osteosarcoma cell proliferation and promotes apoptosis. Asian Pac J Cancer Prev 2013; 14: 2311-5.
30.
Cai H, Xue Y, Wang P, et al. The long noncoding RNA TUG1 regulates blood-tumor barrier permeability by targeting miR-144. Oncotarget 2015; 6: 19759-79.
31.
Liu Q, Sun S, Yu W, et al. Altered expression of long non-coding RNAs during genotoxic stress-induced cell death in human glioma cells. J Neurooncol 2015; 122: 283-92.
32.
Wang Y, Bu P, Li F, et al. [Effects of miR-382 on cell migration, invasion and proliferation of gastric cancer cell lines MGC-803]. Zhonghua Yi Xue Za Zhi 2017; 97: 612-5.
33.
Ishimoto T, Sugihara H, Watanabe M, et al. Macrophage-derived reactive oxygen species suppress miR-328 targeting CD44 in cancer cells and promote redox adaptation. Carcinogenesis 2014; 35: 1003-11.
34.
Jang B I, Li Y, Graham DY, et al. The role of CD44 in the pathogenesis, diagnosis, and therapy of gastric cancer. Gut Liver 2011; 5: 397-405.
35.
Nagano O, Murakami D, Hartmann D, et al. Cell-matrix interaction via CD44 is independently regulated by different metalloproteinases activated in response to extracellular Ca(2+) influx and PKC activation. J Cell Biol 2004; 165: 893-902.
36.
Dalerba P, Dylla SJ, Park IK, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA 2007; 104: 10158-63.
37.
Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 2005; 65: 10946-51.
38.
Hirata K, Suzuki H, Imaeda H, et al. CD44 variant 9 expression in primary early gastric cancer as a predictive marker for recurrence. Br J Cancer 2013; 109: 379-86.
39.
Ishimoto T, Izumi D, Watanabe M, et al. Chronic inflammation with Helicobacter pylori infection is implicated in CD44 overexpression through miR-328 suppression in the gastric mucosa. J Gastroenterol 2015; 50: 751-7.
40.
Ishimoto T, Nagano O, Yae T, et al. CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth. Cancer Cell 2011; 19: 387-400.
41.
Hasita H, Komohara Y, Okabe H, et al. Significance of alternatively activated macrophages in patients with intrahepatic cholangiocarcinoma. Cancer Sci 2010; 101: 1913-9.
42.
Zeilstra J, Joosten SP, Dokter M, Verwiel E, Spaargaren M, Pals ST. Deletion of the WNT target and cancer stem cell marker CD44 in Apc(Min/+) mice attenuates intestinal tumorigenesis. Cancer Res 2008; 68: 3655-61.
43.
Chen Y, Fu Z, Xu S, Xu Y, Xu P. The prognostic value of CD44 expression in gastric cancer: a meta-analysis. Biomed Pharmacother 2014; 68: 693-7.
44.
Winder T, Ning Y, Yang D, et al. Germline polymorphisms in genes involved in the CD44 signaling pathway are associated with clinical outcome in localized gastric adenocarcinoma. Int J Cancer 2011; 129: 1096-104.
45.
Jang BI, Li Y, Graham DY, Cen P. The role of CD44 in the pathogenesis, diagnosis, and therapy of gastric cancer. Gut Liver 2011; 5: 397-405.
46.
Nagano O, Saya H. Mechanism and biological significance of CD44 cleavage. Cancer Sci 2004; 95: 930-5.
Share
RELATED ARTICLE
| eISSN: | 1896-9151 |
| ISSN: | 1734-1922 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
