Abstract
Purpose
Gastric cancer (GC) is caused by environmental factors and genetic changes of protein-coding- and non-coding sequences, which entail short non-coding RNAs (microRNAs) and long non-coding RNAs (lncRNAs). DLEU1 (deleted in lymphocytic leukemia 1), as an effective lncRNA located on chromosome 14.3q 13, modulates the nuclear factor-kB (NF-kB) signaling pathway. This gene usually plays an oncogenic role in the tumorigenesis of multiple types of cancer. The present study examined the expression level of DLEU1 and its association with clinical-pathological characteristics in GC.
Methods
Total RNA of 100 specimens was extracted by TRIzol reagent. After cDNA synthesis, qRT-PCR analysis was performed to measure the expression level of the DLEU1 gene and the obtained data were analyzed by SPSS 16.0.
Results
The relative expression level of DLEU1 significantly increased in tumor specimens compared to the normal tumor margin specimens. The biomarker index of lncRNA DLEU1 was 0.7 in tumor tissues. The observed high expression level of DLEU1 was pertinent to the pathological progressive TNM stage, lymph node metastasis, differentiation degree, patient’s age and lifestyle, and Helicobacter pylori infection in GC patients.
Conclusion
The obtained findings suggested that DLEU1 acts as an oncogene in GC and might be a new target for gene therapy of GC.
Similar content being viewed by others
Availability of Data and Material
The data were available if requested by the editor and reviewers.
References
Sitarz R, Skierucha M, Mielko J, Offerhaus GJA, Maciejewski R, et al. Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer Manag Res. 2018;10:239–48.
Cislo M, Filip AA, Offerhaus GJA, Cisel B, Rawicz-Pruszynski K, et al. Distinct molecular subtypes of gastric cancer: from Lauren to molecular pathology. Oncotarget. 2018;9:19427–42.
Rahman R, Asombang AW, Ibdah JA. Characteristics of gastric cancer in Asia. World J Gastroenterol. 2014;20:4483–90.
Skierucha M, Milne AN, Offerhaus GJ, Polkowski WP, Maciejewski R, et al. Molecular alterations in gastric cancer with special reference to the early-onset subtype. World J Gastroenterol. 2016;22:2460–74.
Kazemzadeh M, Safaralizadeh R, Orang AV. LncRNAs: emerging players in gene regulation and disease pathogenesis. J Genet. 2015;94:771–84.
Kazemzadeh M, Safaralizadeh R, Feizi MA, Ravanbakhsh R, Somi MH, et al. LOC100287225, novel long intergenic non-coding RNA, misregulates in colorectal cancer. Cancer Biomark. 2016;16:499–505.
Kazemzadeh M, Safaralizadeh R, Feizi MA, Somi MH, Shokoohi B. Misregulation of the dependence receptor DCC and its upstream lincRNA, LOC100287225, in colorectal cancer. Tumori. 2017;103:40–3.
Dastmalchi N, Safaralizadeh R, Nargesi MM. LncRNAs: potential novel prognostic and diagnostic biomarkers in colorectal cancer. Curr Med Chem. 2020;27:5067–77.
Mohammadrezakhani H, Baradaran B, Shanehbandi D, Asadi M, Hashemzadeh S, et al. Overexpression and clinicopathological correlation of long noncoding RNA TMPO-AS1 in colorectal cancer patients. J Gastrointest Cancer. 2020;51:952–6.
Dastmalchi N, Khojasteh SMB, Nargesi MM, Safaralizadeh R. The correlation between lncRNAs and Helicobacter pylori in gastric cancer. Pathog Dis. 2019;77(9):ftaa004.
Behzadi S, Baradaran B, Hosseinpourfeizi MA, Dastmalchi N, Rajabi A, et al. BC032913 as a novel antisense non-coding RNA is downregulated in gastric cancer. J Gastrointest Cancer. 2021;52:928–31.
Sanchez Calle A, Kawamura Y, Yamamoto Y, Takeshita F, Ochiya T. Emerging roles of long non-coding RNA in cancer. Cancer Sci. 2018;109:2093–100.
de Giorgio A, Krell J, Harding V, Stebbing J, Castellano L. Emerging roles of competing endogenous RNAs in cancer: insights from the regulation of PTEN. Mol Cell Biol. 2013;33:3976–82.
Liu F, Chen N, Gong Y, Xiao R, Wang W, et al. The long non-coding RNA NEAT1 enhances epithelial-to-mesenchymal transition and chemoresistance via the miR-34a/c-Met axis in renal cell carcinoma. Oncotarget. 2017;8:62927–38.
Garding A, Bhattacharya N, Claus R, Ruppel M, Tschuch C, et al. Epigenetic upregulation of lncRNAs at 13q14.3 in leukemia is linked to the In Cis downregulation of a gene cluster that targets NF-kB. PLoS Genet. 2013;9:e1003373.
Li X, Li Z, Liu Z, Xiao J, Yu S, et al. Long non-coding RNA DLEU1 predicts poor prognosis of gastric cancer and contributes to cell proliferation by epigenetically suppressing KLF2. Cancer Gene Ther. 2018;25:58–67.
Mao X, Su Z, Mookhtiar AK. Long non-coding RNA: a versatile regulator of the nuclear factor-kappaB signalling circuit. Immunology. 2017;150:379–88.
Dowd AA, Homeida S, Elkarem HA. Detection of chromosome 13 (13q14) deletion among Sudanese patients with multiple myeloma using a molecular genetics fluorescent in situ hybridization technique (FISH). Malays J Pathol. 2015;37:95–100.
Wu Q, Guo L, Jiang F, Li L, Li Z, et al. Analysis of the miRNA-mRNA-lncRNA networks in ER+ and ER- breast cancer cell lines. J Cell Mol Med. 2015;19:2874–87.
Lee S, Luo W, Shah T, Yin C, O’Connell T, et al. The effects of DLEU1 gene expression in Burkitt lymphoma (BL): potential mechanism of chemoimmunotherapy resistance in BL. Oncotarget. 2017;8:27839–53.
Zhang R, Xia LQ, Lu WW, Zhang J, Zhu JS. LncRNAs and cancer. Oncol Lett. 2016;12:1233–9.
Bhan A, Soleimani M, Mandal SS. Long noncoding RNA and cancer: a new paradigm. Cancer Res. 2017;77:3965–81.
Liu C, Tian X, Zhang J, Jiang L. Long non-coding RNA DLEU1 promotes proliferation and invasion by interacting with miR-381 and enhancing HOXA13 expression in cervical cancer. Front Genet. 2018;9:629.
Chen X, Zhang C, Wang X. Long noncoding RNA DLEU1 aggravates osteosarcoma carcinogenesis via regulating the miR-671-5p/DDX5 axis. Artif Cells Nanomed Biotechnol. 2019;47:3322–8.
Liu T, Han Z, Li H, Zhu Y, Sun Z, et al. LncRNA DLEU1 contributes to colorectal cancer progression via activation of KPNA3. Mol Cancer. 2018;17:118.
Wang LL, Sun KX, Wu DD, Xiu YL, Chen X, et al. DLEU1 contributes to ovarian carcinoma tumourigenesis and development by interacting with miR-490-3p and altering CDK1 expression. J Cell Mol Med. 2017;21:3055–65.
Zhang S, Guan Y, Liu X, Ju M, Zhang Q. Long non-coding RNA DLEU1 exerts an oncogenic function in non-small cell lung cancer. Biomed Pharmacother. 2019;109:985–90.
Nishiyama K, Maruyama R, Niinuma T, Kai M, Kitajima H, et al. Screening for long noncoding RNAs associated with oral squamous cell carcinoma reveals the potentially oncogenic actions of DLEU1. Cell Death Dis. 2018;9:826.
Yue G, Chen C, Bai L, Wang G, Huang Y, et al. Knockdown of long noncoding RNA DLEU1 suppresses the progression of renal cell carcinoma by downregulating the Akt pathway. Mol Med Rep. 2019;20:4551–7.
Pang B, Sui S, Wang Q, Wu J, Yin Y, et al. Upregulation of DLEU1 expression by epigenetic modification promotes tumorigenesis in human cancer. J Cell Physiol. 2019;234:17420–32.
Acknowledgements
The authors would like to thank the staff of Immunology Research Center, Tabriz University of Medical Sciences, for their assistance throughout this study.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethics Approval and Consent to Participate
The present study was approved by the Ethics Committee of Tabriz University of Medical Sciences, Tabriz, Iran (approval number: IR.TBZMED.REC.1397.638, date: 5 November 2018). All patients signed the written informed consent form. All participants signed the informed consent.
Consent for Publication
Not applicable.
Conflict of Interest
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Ghodrati, R., Safaralizadeh, R., Dastmalchi, N. et al. Overexpression of lncRNA DLEU1 in Gastric Cancer Tissues Compared to Adjacent Non-Tumor Tissues. J Gastrointest Canc 53, 990–994 (2022). https://doi.org/10.1007/s12029-021-00733-8
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12029-021-00733-8