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The Expression Analysis of Long Non-coding RNAs Related to Wnt/β-Catenin Signaling in Pancreatic Cancer Patients

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Abstract

Background The oncogenic Wnt/β-catenin signaling plays a critical role in carcinogenesis, prognosis, and resistance to therapy. Pancreatic cancer (PC) has high mortality because of its poor prognosis. Several studies have suggested that lncRNAs are directly involved in the development and progression of PC as well as in Wnt/β-catenin signaling. In this study, we investigated and compared the expression of Wnt/β-catenin signaling-related ZFAS1 and HCG11 lncRNAs, and their targets, CTNNB1 and IGF2BP1 genes in the blood of patients with PC and healthy individuals. A total of 47 PC patients and 50 healthy individuals participated in this study. RNA was extracted from the peripheral blood samples of participants, and cDNA was synthesized. The expression level of the selected genes was quantified by real-time PCR. The expression of HCG11 lncRNA and CTNNB1 genes in patients with PC was significantly upregulated compared to healthy individuals, and the expression of the ZFAS1 lncRNA was significantly downregulated. According to the analysis of the ROC curve, the diagnostic powers of ZFAS1 and CTNNB1 in PC were 0.67 and 0.69, respectively. Altogether, the present study suggests a role for ZFAS1 and HCG11 lncRNAs and CTNNB1 and IGF2BP1 in the pathogenesis of pancreatic cancer. Moreover, the peripheral expression of these lncRNAs may be useful as potential biomarkers for PC.

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References

  • Betson N, Hajahmed M, Gebretsadek T, Ndebele K, Ahmad HA, Tchounwou PB, Spiegelman VS, Noubissi FK (2022) Inhibition of insulin-like growth factor 2 mRNA-binding protein 1 sensitizes colorectal cancer cells to chemotherapeutics. FASEB BioAdvances 4:816–829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cavard C, Colnot S, Audard V, Benhamouche S, Finzi L, Torre C, Grimber G, Godard C, Terris B, Perret C (2008) Wnt/β-catenin pathway in hepatocellular carcinoma pathogenesis and liver physiology. Future Oncol 4:647–660

    Article  CAS  PubMed  Google Scholar 

  • Chiurillo MA (2015) Role of the Wnt/β-catenin pathway in gastric cancer: an in-depth literature review. World J Exp Med 5:84–102

    Article  PubMed  PubMed Central  Google Scholar 

  • Cui Y, Zhang F, Zhu C, Geng L, Tian T, Liu H (2017) Upregulated lncRNA SNHG1 contributes to progression of non-small cell lung cancer through inhibition of miR-101-3p and activation of Wnt/β-catenin signaling pathway. Oncotarget 8:17785–17794

    Article  PubMed  PubMed Central  Google Scholar 

  • Fu PF, Zheng X, Fan X, Lin AF (2019) Role of cytoplasmic lncRNAs in regulating cancer signaling pathways. J Zhejiang Univ Sci B 20:1–8

    Article  PubMed  PubMed Central  Google Scholar 

  • Gekas C, D’Altri T, Aligué R, González J, Espinosa L, Bigas A (2016) β-Catenin is required for T-cell leukemia initiation and MYC transcription downstream of Notch1. Leukemia 30:2002–2010

    Article  CAS  PubMed  Google Scholar 

  • Glaß M, Misiak D, Bley N, Müller S, Hagemann S, Busch B, Rausch A, Hüttelmaier S (2021) IGF2BP1, a conserved regulator of RNA turnover in cancer. Front Mol Biosci. https://doi.org/10.3389/fmolb.2021.632219

    Article  PubMed  PubMed Central  Google Scholar 

  • Han S, Li DZ, Xiao MF (2019) LncRNA ZFAS1 serves as a prognostic biomarker to predict the survival of patients with ovarian cancer. Exp Ther Med 18:4673–4681

    CAS  PubMed  PubMed Central  Google Scholar 

  • He A, He S, Li X, Zhou L (2019) ZFAS1: A novel vital oncogenic lncRNA in multiple human cancers. Cell Prolif 52:e12513

    Article  PubMed  Google Scholar 

  • Hu XY, Hou PF, Li TT, Quan HY, Li ML, Lin T, Liu JJ, Bai J, Zheng JN (2018) The roles of Wnt/β-catenin signaling pathway related lncRNAs in cancer. Int J Biol Sci 14:2003–2011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jing S, Tian J, Zhang Y, Chen X, Zheng S (2020) Identification of a new pseudogenes/lncRNAs-hsa-miR-26b-5p-COL12A1 competing endogenous RNA network associated with prognosis of pancreatic cancer using bioinformatics analysis. Aging (albany NY) 12:19107–19128

    Article  CAS  PubMed  Google Scholar 

  • Kolenda T, Guglas K, Kopczyńska M, Teresiak A, Bliźniak R, Mackiewicz A, Lamperska K, Mackiewicz J (2019) Oncogenic role of ZFAS1 lncRNA in head and neck squamous cell carcinomas. Cells 8:366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Y, Zhu G, Zeng W, Wang J, Li Z, Wang B, Tian B, Lu D, Zhang X, Gao G, Li L (2017) Long noncoding RNA AB073614 promotes the malignance of glioma by activating Wnt/β-catenin signaling through downregulating SOX7. Oncotarget 8:65577–65587

    Article  PubMed  PubMed Central  Google Scholar 

  • Li W, Han S, Hu P, Chen D, Zeng Z, Hu Y, Xu F, Tang J, Wang F, Zhao Y, Huang M, Zhao G (2021) LncRNA ZNFTR functions as an inhibitor in pancreatic cancer by modulating ATF3/ZNF24/VEGFA pathway. Cell Death Dis 12:830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu H, Li J, Koirala P, Ding X, Chen B, Wang Y, Wang Z, Wang C, Zhang X, Mo YY (2016) Long non-coding RNAs as prognostic markers in human breast cancer. Oncotarget 7:20584–20596

    Article  PubMed  PubMed Central  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408

    Article  CAS  PubMed  Google Scholar 

  • Nie F, Yu X, Huang M, Wang Y, Xie M, Ma H, Wang Z, De W, Sun M (2017) Long noncoding RNA ZFAS1 promotes gastric cancer cells proliferation by epigenetically repressing KLF2 and NKD2 expression. Oncotarget 8:38227–38238

    Article  PubMed  Google Scholar 

  • O’Brien SJ, Fiechter C, Burton J, Hallion J, Paas M, Patel A, Patel A, Rochet A, Scheurlen K, Gardner S, Eichenberger M, Sarojini H, Srivastava S, Rai S, Kalbfleisch T, Polk HC, Galandiuk S (2021) Long non-coding RNA ZFAS1 is a major regulator of epithelial–mesenchymal transition through miR-200/ZEB1/E-cadherin, vimentin signaling in colon adenocarcinoma. Cell Death Discovery 7:61

    Article  PubMed  PubMed Central  Google Scholar 

  • Pan L, Liang W, Fu M, Huang ZH, Li X, Zhang W, Zhang P, Qian H, Jiang PC, Xu WR, Zhang X (2017) Exosomes-mediated transfer of long noncoding RNA ZFAS1 promotes gastric cancer progression. J Cancer Res Clin Oncol 143:991–1004

    Article  CAS  PubMed  Google Scholar 

  • Ram Makena M, Gatla H, Verlekar D (2019) Wnt/β-catenin signaling: the culprit in pancreatic carcinogenesis and therapeutic resistance. Int J Mol Sci 20:4242

    Article  PubMed  PubMed Central  Google Scholar 

  • Rao M, Xu S, Zhang Y, Liu Y, Luan W, Zhou J (2021) Long non-coding RNA ZFAS1 promotes pancreatic cancer proliferation and metastasis by sponging miR-497-5p to regulate HMGA2 expression. Cell Death Dis 12:859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Su Y, Hou W, Zhang C, Ji P, Hu R, Zhang Q, Wang Y, Li P, Zhang H, Chen Y, Zhang X, Zhang M (2022) Long non-coding RNA ZFAS1 regulates cell proliferation and invasion in cervical cancer via the miR-190a-3p/KLF6 axis. Bioengineered 13:3840–3851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wan BS, Cheng M, Zhang L (2019) Insulin-like growth factor 2 mRNA-binding protein 1 promotes cell proliferation via activation of AKT and is directly targeted by microRNA-494 in pancreatic cancer. World J Gastroenterol 25:6063–6076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang L, Ruan Y, Wu X, Zhou X (2022) lncRNA ZFAS1 promotes HMGCR mRNA stabilization via binding U2AF2 to modulate pancreatic carcinoma lipometabolism. J Immunol Res 2022:4163198

    Article  PubMed  PubMed Central  Google Scholar 

  • Xie D, Li S, Wang X, Fang L (2023) lncRNA HCG11 suppresses cell proliferation in hormone receptor-positive breast cancer via SRSF1/β-catenin. Aging (albany NY) 15:179–192

    Article  CAS  PubMed  Google Scholar 

  • Xu W, He L, Li Y, Tan Y, Zhang F, Xu H (2018) Silencing of lncRNA ZFAS1 inhibits malignancies by blocking Wnt/β-catenin signaling in gastric cancer cells. Biosci Biotechnol Biochem 82:456–465

    Article  CAS  PubMed  Google Scholar 

  • Xu J, Xu W, Yang X, Liu Z, Sun Q (2021) LncRNA HCG11/miR-579-3p/MDM2 axis modulates malignant biological properties in pancreatic carcinoma via Notch/Hes1 signaling pathway. Aging (albany NY) 13:16471–16484

    Article  CAS  PubMed  Google Scholar 

  • Xu Y, Yu X, Sun Z, He Y, Guo W (2022) Roles of lncRNAs mediating Wnt/β-catenin signaling in HCC. Front Oncol 12:831366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan X, Zhao Q, Zhang Y, Xue M (2021) The role and mechanism of HLA complex group 11 in cancer. Biomed Pharmacother 143:112210

    Article  CAS  PubMed  Google Scholar 

  • Zeng G, Germinaro M, Micsenyi A, Monga NK, Bell A, Sood A, Malhotra V, Sood N, Midda V, Monga DK, Kokkinakis DM, Monga SP (2006) Aberrant Wnt/beta-catenin signaling in pancreatic adenocarcinoma. Neoplasia 8:279–289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhai S, Xu Z, Xie J, Zhang J, Wang X, Peng C, Li H, Chen H, Shen B, Deng X (2021) Epigenetic silencing of LncRNA LINC00261 promotes c-myc-mediated aerobic glycolysis by regulating miR-222-3p/HIPK2/ERK axis and sequestering IGF2BP1. Oncogene 40:277–291

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Wang X (2020) Targeting the Wnt/β-catenin signaling pathway in cancer. J Hematol Oncol 13:165

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang H, Huang H, Xu X, Wang H, Wang J, Yao Z, Xu X, Wu Q, Xu F (2019) LncRNA HCG11 promotes proliferation and migration in gastric cancer via targeting miR-1276/CTNNB1 and activating Wnt signaling pathway. Cancer Cell Int 19:350

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Zhang J, Mao L, Li X (2020) Long noncoding RNA HCG11 inhibited growth and invasion in cervical cancer by sponging miR-942-5p and targeting GFI1. Cancer Med 9:7062–7071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang W-T, Zhang J-J, Shao Q, Wang Y-K, Jia J-P, Qian B, Tian X-W, Yan W-J, Zhang W-T, Zhang J-J, Shao Q, Wang Y-K, Jia J-P, Qian B, Tian X-W, Yan W-J, Zhang W-T, Zhang J-J, Shao Q, Wang Y-K, Jia J-P, Qian B, Tian X-W, Yan W-J, Zhang W-T, Zhang J-J, Shao Q, Wang Y-K, Jia J-P, Qian B, Tian X-W, Yan W-J (2022) FGD5-AS1 is an oncogenic lncRNA in pancreatic cancer and regulates the Wnt/β-catenin signaling pathway via miR-577. Oncol Rep 47:21

    Article  PubMed  Google Scholar 

  • Zhou W, Chen L, Li C, Huang R, Guo M, Ning S, Ji J, Guo X, Lou G, Jia X, Zhao J, Luo F, Li C, Qu Z, Yu S, Tai S (2020) The multifaceted roles of long noncoding RNAs in pancreatic cancer: an update on what we know. Cancer Cell Int 20:41

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu T, Wang Z, Wang G, Hu Z, Ding H, Li R, Sun J (2021) Long non-coding RNA ZFAS1 promotes the expression of EPAS1 in gastric cardia adenocarcinoma. J Adv Res 28:7–15

    Article  CAS  PubMed  Google Scholar 

  • Zhuo ZL, Xian HP, Sun YJ, Long Y, Liu C, Liang B, Zhao XT (2022) Long noncoding RNA ZNFX1-AS1 promotes the invasion and proliferation of gastric cancer cells by regulating LIN28 and CAPR1N1. World J Gastroenterol 28:4973–4992

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors gratefully acknowledge the late Dr. Roya Amirinejad who loved science for her valuable laboratory supports as well as the contribution of the patients, participants, and institutions in this study. This work was supported by the Shahid Beheshti University, Tehran, IR Iran and Iran University of Medical Sciences, Tehran, Iran.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran

    Fatemeh Katoozian & Zeinab Shirvani-Farsani

  2. Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

    Zahra Abedi Kichi

  3. Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians University, Munich, Germany

    Zahra Abedi Kichi

  4. Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran

    Roya Sharifi

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  1. Fatemeh Katoozian
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  2. Zahra Abedi Kichi
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  4. Zeinab Shirvani-Farsani
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Contributions

FK and ZAK wrote the manuscript, analyzed the data, and performed the experiment. ZSF and RS designed the study and revised the manuscript. All the authors read and approved the final manuscript.

Corresponding authors

Correspondence to Roya Sharifi or Zeinab Shirvani-Farsani.

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This study was approved by the Ethnics Committees of Iran University of Medical Sciences (IR.IUMS.REC.1397.1126).

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Katoozian, F., Abedi Kichi, Z., Sharifi, R. et al. The Expression Analysis of Long Non-coding RNAs Related to Wnt/β-Catenin Signaling in Pancreatic Cancer Patients. Biochem Genet (2024). https://doi.org/10.1007/s10528-024-10779-5

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