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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2018 | Research

LncRNA-TUSC7/miR-224 affected chemotherapy resistance of esophageal squamous cell carcinoma by competitively regulating DESC1

Authors: Zhi-wei Chang, Yong-xu Jia, Wei-jie Zhang, Li-jie Song, Ming Gao, Ming-jun Li, Rui-hua Zhao, Jing Li, Ya-li Zhong, Qiao-zhi Sun, Yan-ru Qin

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2018

Abstract

Background

This study aims to clarify the underlying mechanism for the tumor suppressive function of lnc TUSC7 in chemotherapy resistance of esophageal squamous cell carcinoma (ESCC).

Methods

TUSC7, miR-224 and DESC1 expressions in ESCC tissues and cells were detected by qRT-PCR. Protein level of DESC1, EGFR and p-AKT were observed by Western blot. Overall survival was calculated using the Kaplan-Meier method. Dual-luciferase reporter gene assay and RIP assay were used to comfirm TUSC7 binding to miR-224, and miR-224 binding to DESC1. Cell proliferation, apoptosis, and colony formation was detected by MTT, Flow Cytometry and Colony formation assays.

Results

TUSC7 was downregulated in ESCC tissues and cells, and low TUSC7 indicated worse overall survival. The analysis of bioinformatics softwares showed that TUSC7 specifically bound to miR-224, and we proved miR-224 was upregulated in ESCC and negatively correlated with TUSC7 expression. Overexpression of TUSC7/inhibition of miR-224 suppressed cell proliferation, colony formation and chemotherapy resistance of ESCC cells, and promoted cell apoptosis. In addition, we confirmed that miR-224 specifically bound to DESC1, and negatively correlated with DESC1. TUSC7 suppressed the proliferation and chemotherapy resistance of ESCC cells by increasing DESC1 expression via inhibiting miR-224. We also confirmed DESC1 inhibited chemotherapy resistance of ESCC cells via EGFR/AKT. Finally, in vivo experiments demonstrated that overexpression of TUSC7 decreased tumor growth and chemotherapy resistance.

Conclusion

These findings suggested TUSC7 suppressed chemotherapy resistance of ESCC by downregulating miR-224 to modulate DESC1/EGFR/AKT pathway.

Ferlay J, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86.CrossRefPubMed

Arnold M, et al. Global incidence of oesophageal cancer by histological subtype in 2012. Gut. 2015;64(3):381–7.CrossRefPubMed

Chen J, et al. Intensity-modulated radiotherapy combined with paclitaxel and platinum treatment regimens in locally advanced esophageal squamous cell carcinoma. Clin Transl Oncol. 2018;20(3):411–19.

Akiyama Y, et al. Investigation of operative outcomes of thoracoscopic esophagectomy after triplet chemotherapy with docetaxel, cisplatin, and 5-fluorouracil for advanced esophageal squamous cell carcinoma. Surg Endosc. 2018;32(1):391–9.

Yen YC, et al. Effectiveness of esophagectomy in patients with thoracic esophageal squamous cell carcinoma receiving definitive radiotherapy or concurrent chemoradiotherapy through intensity-modulated radiation therapy techniques. Cancer. 2017;123(11):2043–53.CrossRefPubMed

Burt BM, et al. Utility of adjuvant chemotherapy after neoadjuvant Chemoradiation and Esophagectomy for esophageal cancer. Ann Surg. 2017;266(2):297–304.CrossRefPubMed

Pasquali S, et al. Survival after neoadjuvant and adjuvant treatments compared to surgery alone for Resectable esophageal carcinoma: a network meta-analysis. Ann Surg. 2017;265(3):481–91.CrossRefPubMed

Viloria CG, et al. Human DESC1 serine protease confers tumorigenic properties to MDCK cells and it is upregulated in tumours of different origin. Br J Cancer. 2007;97(2):201–9.CrossRefPubMedPubMedCentral

Kyrieleis OJ, et al. Crystal structure of the catalytic domain of DESC1, a new member of the type II transmembrane serine proteinase family. FEBS J. 2007;274(8):2148–60.CrossRefPubMed

10.

Zinovyeva MV, et al. Identification of some human genes oppositely regulated during esophageal squamous cell carcinoma formation and human embryonic esophagus development. Dis Esophagus. 2010;23(3):260–70.CrossRefPubMed

11.

Ng HY, et al. DESC1, a novel tumor suppressor, sensitizes cells to apoptosis by downregulating the EGFR/AKT pathway in esophageal squamous cell carcinoma. Int J Cancer. 2016;138(12):2940–51.CrossRefPubMed

12.

Koshizuka K, et al. Involvement of aberrantly expressed microRNAs in the pathogenesis of head and neck squamous cell carcinoma. Cancer Metastasis Rev. 2017;36(3):525–45.

13.

Tanaka K, et al. miR-27 is associated with chemoresistance in esophageal cancer through transformation of normal fibroblasts to cancer-associated fibroblasts. Carcinogenesis. 2015;36(8):894–903.CrossRefPubMed

14.

Lu M, et al. MicroRNA and target mRNA selection through invasion and cytotoxicity cell modeling and bioinformatics approaches in esophageal squamous cell carcinoma. Oncol Rep. 2017;38(2):1181–9.CrossRefPubMed

15.

Sharma P, Saini N, Sharma R. miR-107 functions as a tumor suppressor in human esophageal squamous cell carcinoma and targets Cdc42. Oncol Rep. 2017;37(5):3116–27.CrossRefPubMed

16.

He X, et al. Expression and role of oncogenic miRNA-224 in esophageal squamous cell carcinoma. BMC Cancer. 2015;15:575.CrossRefPubMedPubMedCentral

17.

Betel D, et al. The microRNA.Org resource: targets and expression. Nucleic Acids Res. 2008;36(Database issue):D149–53.PubMed

18.

Wang X, et al. Silencing of long noncoding RNA MALAT1 by miR-101 and miR-217 inhibits proliferation, migration, and invasion of esophageal squamous cell carcinoma cells. J Biol Chem. 2015;290(7):3925–35.CrossRefPubMed

19.

Rinn JL, Chang HY. Genome regulation by long noncoding RNAs. Annu Rev Biochem. 2012;81. https://doi.org/10.1146/annurev-biochem-051410-092902.

20.

Xu J, Zhang R, Zhao J. The novel long noncoding RNA TUSC7 inhibits proliferation by sponging MiR-211 in colorectal cancer. Cell Physiol Biochem. 2017;41(2):635–44.CrossRefPubMed

21.

Shang C, et al. Long non-coding RNA TUSC7, a target of miR-23b, plays tumor-suppressing roles in human gliomas. Front Cell Neurosci. 2016;10:235.CrossRefPubMedPubMedCentral

22.

Qi P, et al. Reciprocal repression between TUSC7 and miR-23b in gastric cancer. Int J Cancer. 2015;137(6):1269–78.CrossRefPubMed

23.

Kan R, et al. NF-κB p65 subunit is modulated by latent transforming growth factor-β binding protein 2 (LTBP2) in nasopharyngeal carcinoma HONE1 and HK1 cells. PLoS One. 2015;10(5):e0127239.CrossRefPubMedPubMedCentral

24.

Zhang H, et al. AST1306, a potent EGFR inhibitor, antagonizes ATP-binding cassette subfamily G member 2-mediated multidrug resistance. Cancer Lett. 2014;350(1-2):61–8.CrossRefPubMed

25.

Zhuang J, et al. TGFbeta1 promotes gemcitabine resistance through regulating the LncRNA-LET/NF90/miR-145 signaling Axis in bladder cancer. Theranostics. 2017;7(12):3053–67.CrossRefPubMedPubMedCentral

26.

Chen DL, et al. Long noncoding RNA XIST expedites metastasis and modulates epithelial-mesenchymal transition in colorectal cancer. Cell Death Dis. 2017;8(8):e3011.CrossRefPubMedPubMedCentral

27.

Miao X, et al. Down-regulation of microRNA-224 -inhibites growth and epithelial-to-mesenchymal transition phenotype -via modulating SUFU expression in bladder cancer cells. Int J Biol Macromol. 2018;106:234–40.

28.

He C, et al. Hypoxia-inducible microRNA-224 promotes the cell growth, migration and invasion by directly targeting RASSF8 in gastric cancer. Mol Cancer. 2017;16(1):35.CrossRefPubMedPubMedCentral

29.

Cui R, et al. MicroRNA-224 is implicated in lung cancer pathogenesis through targeting caspase-3 and caspase-7. Oncotarget. 2015;6(26):21802–15.CrossRefPubMedPubMedCentral

30.

Goto Y, et al. Tumour-suppressive microRNA-224 inhibits cancer cell migration and invasion via targeting oncogenic TPD52 in prostate cancer. FEBS Lett. 2014;588(10):1973–82.CrossRefPubMed

31.

Yuan K, et al. Decreased levels of miR-224 and the passenger strand of miR-221 increase MBD2, suppressing maspin and promoting colorectal tumor growth and metastasis in mice. Gastroenterology. 2013;145(4):853–64.e9.CrossRefPubMedPubMedCentral

32.

Song G, et al. Deregulated expression of miR-224 and its target gene: CD59 predicts outcome of diffuse large B-cell lymphoma patients treated with R-CHOP. Curr Cancer Drug Targets. 2014;14(7):659–70.CrossRefPubMed

Title: LncRNA-TUSC7/miR-224 affected chemotherapy resistance of esophageal squamous cell carcinoma by competitively regulating DESC1
Authors: Zhi-wei Chang
Yong-xu Jia
Wei-jie Zhang
Li-jie Song
Ming Gao
Ming-jun Li
Rui-hua Zhao
Jing Li
Ya-li Zhong
Qiao-zhi Sun
Yan-ru Qin
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2018
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-018-0724-4

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Abstract

Background

Methods

Results

Conclusion

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