Small Nuclear RNA 64 (snoRNA64): A novel Tumor Biomarker for Pancreatic Cancer
DOI:
https://doi.org/10.21123/bsj.2023.7135Keywords:
Biomarker, EMT, MET, Metastatic Cancer, PDAC, snoRNA64Abstract
The pancreatic ductal adenocarcinoma (PDAC), which represents over 90% of pancreatic cancer cases,
has the highest proliferative and metastatic rate in comparison to other pancreatic cancer compartments. This
study is designed to determine whether small nucleolar RNA, H/ACA box 64 (snoRNA64) is associated with
pancreatic cancer initiation and progression. Gene expression data from the Gene Expression Omnibus (GEO)
repository have shown that snoRNA64 expression is reduced in primary and metastatic pancreatic cancer as
compared to normal tissues based on statistical analysis of the in Silico analysis. Using qPCR techniques,
pancreatic cancer cell lines include PK-1, PK-8, PK-4, and Mia PaCa-2 with different levels of snoRNA64,
including PK-1, PK-8, PK-4, and Mia PaCa-2. The level of expression is correlated with the cell line epithelial
or mesenchymal characteristics. Cell lines displaying epithelial characteristics such as PK-1, PK-8 show high
levels of snoRNA64 meanwhile, cell lines displaying mesenchymal characteristics such as PK-4, Mia PaCa-2
show low levels of snoRNA64. The level of expression is correlated with the cell line epithelial or
mesenchymal characteristics. After knocking down the PK-8 with high snoRNA64 expression, the epithelial
markers E. cadherin (E-cad) and Cytokeratin-8 (CK-8) are decreased, while mesenchymal markers Vimentin
(Vim), Cytokeratin-19 (CK-19), Metalloprotease -2 (MMP-2), and Metalloprotease-3 (MMP-3) are activated.
Those changes suggest that PK-8 responding to the snoRNA64 knock down protocol and increase in
mesenchymal function. Together, snoRNA64 expression may participate in epithelial to mesenchymal
transition (EMT) and mesenchymal to epithelial transition (MET), in which during metastasis these processes
are crucial. In addition, snoRNA64 may be considered as a potential diagnostic biomarker for both early and
invasive stages of PDAC. And due to its gradual expression decreases, it may be considered a barrier in tumor
progression.
Received 2/3/2022
Revised 22/10/2022
Accepted 23/10/2022
Published Online First 20/3/2023
References
Joanna K, Pawel G,Small Nucleolar RNAs Tell a Different Tale. Trends Genet. 2019; 35(2): 104-117. https://dx.doi.org/10.1016/j.tig.2018.11.005 .
De Zoysa MD, Yu YT. Posttranscriptional RNA pseudouridylation. Enzymes. 2017; 1(41): 151-67. https://dx.doi.org/10.1016/bs.enz.2017.02.001
Cassidy SB, Schwartz S, Miller JL, Driscoll DJ. Prader-willi syndrome. Genet Med. 2012; 14(1): 10-26. https://doi.org/10.1038/gim.0b013e31822bead0
Mourksi NEH, Morin C, Fenouil T, Diaz JJ, Marcel V. snoRNAs Offer Novel Insight and Promising Perspectives for Lung Cancer Understanding and Management . Cells. 2020; 9(3): 541. https://doi.org/10.3390/cells9030541.
Dsouza VL, Adiga D, Sriharikrishnaa S, Suresh PS, Chatterjee A, Kabekkodu SP. Small nucleolar RNA and its potential role in breast cancer–A comprehensive review. Biochim Biophys Acta Rev Cancer. 2021; 1875(1): 188501. https://doi.org/10.1016/j.bbcan.2020.188501 .
Zhou F, Liu Y, Rohde C, Pauli C, Gerloff D, Köhn M, et al. AML1-ETO requires enhanced C/D box snoRNA/RNP formation to induce self-renewal and leukaemia. Nat Cell Biol. 2017; 19(7): 844–855. https://doi.org/10.1038/ncb3563 .
Yi C, Wan X, Zhang Y, Fu F, Zhao C, Qin R, et al. SNORA42 enhances prostate cancer cell viability, migration and EMT and is correlated with prostate cancer poor prognosis. Int J Biochem Cell Biol. 2018; 1(102): 138-50. https://doi.org/10.1016/j.biocel.2018.07.009 .
Kitagawa T, Taniuchi K, Tsuboi M, Sakaguchi M, Kohsaki T, Okabayashi T, et al. Circulating pancreatic cancer exosomal RNAs for detection of pancreatic cancer. Mol Oncol. 2019; 13(2): 212-227. https://doi.org/10.1002/1878-0261.12398
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020; 70(1): 7–30. https://doi.org/10.3322/caac.21590 .
Kleeff J, Korc M, Apte M, La Vecchia C, Johnson CD, Biankin A V., et al. Pancreatic cancer. Nat Rev Dis Primers. 2016; 2(1): 1–22. https://doi.org/10.1038/nrdp.2016.22 .
Pittman ME, Rao R, Hruban RH. Classification, morphology, molecular pathogenesis, and outcome of premalignant lesions of the pancreas. Arch Pathol Lab Med. 2017; 141(12): 1606-14. https://doi.org/10.5858/arpa.2016-0426-RA .
Sarantis P, Koustas E, Papadimitropoulou A, Papavassiliou AG, Karamouzis M V. Pancreatic ductal adenocarcinoma: Treatment hurdles, tumor microenvironment and immunotherapy. World J Gastrointest Onco. 2020; 12(2): 173–181. https://doi.org/10.4251/wjgo.v12.i2.173 .
Grant TJ, Hua K, Singh A. Molecular Pathogenesis of Pancreatic Cancer. In: Progress in Molecular Biology and Translational Science. Prog Mol Biol Transl Sci. 2016; 144: 241–75. https://doi.org/10.1016/bs.pmbts.2016.09.008 .
Mas L, Lupinacci RM, Cros J, Bachet JB, Coulet F, Svrcek M. Intraductal papillary mucinous carcinoma versus conventional pancreatic ductal adenocarcinoma: A comprehensive review of clinical-pathological features, outcomes, and molecular insights. Int J Mol Sci. 2021; 22(13): 6756-. https://doi.org/10.3390/ijms22136756
Puckett Y, Sharma B, Kasi A. Intraductal Papillary Mucinous Cancer Of The Pancreas. StatPearls. 2022. https://www.ncbi.nlm.nih.gov/books/NBK507779/
McCann KL, Kavari SL, Burkholder AB, Phillips BT, Hall TMT. H/ACA snoRNA levels are regulated during stem cell differentiation. Nucleic Acids Res. 2020; 48(15): 8686-8703. https://doi.org/10.1093/nar/gkaa612 .
Steinbusch MMF, Fang Y, Milner PI, Clegg PD, Young DA, Welting TJM, et al. Serum snoRNAs as biomarkers for joint ageing and post traumatic osteoarthritis. Sci Rep. 2017; 7: 43558. https://doi.org/10.1038/srep43558 .
Roake CM, Artandi SE. Regulation of human telomerase in homeostasis and disease. Nat Rev Mol Cell Biol. 2020 Jul; 21(7): 384-97. https://doi.org/10.1038/s41580-020-0234-z
Hiraoka N, Yamazaki-Itoh R, Ino Y, Mizuguchi Y. CXCL17 and ICAM2 are associated with a potential anti-tumor immune response in early intraepithelial stages of human pancreatic carcinogenesis. Gastroenterology 2011 Jan; 140(1): 310-21. https://doi.org/10.1053/j.gastro.2010.10.009 .
Vila-Navarro E, Duran-Sanchon S, Vila-Casadesús M, Moreira L, Ginès À, Cuatrecasas M, et al. Novel circulating miRNA signatures for early detection of pancreatic neoplasia. Clin Transl Gastroentero. 2019; 10(4): e00029. https://doi.org/10.14309/ctg.0000000000000029
Zhang X, Shi S, Zhang B, Ni Q, Yu X, Xu J. Circulating biomarkers for early diagnosis of pancreatic cancer: facts and hopes. Am J Cancer Res. 2018; 8(3): 332-353
Farivar S, Amirinejad R, Naghavi gargari B, Hassani SB, Shirvani farsani Z. In Silico Analysis of Regulatory Elements of the Vitamin D Receptor. Baghdad Sci J. 2020. 17(2): 463-470. https://doi.org/10.21123/bsj.2020.17.2.0463
Muraki T, Jang KT, Reid MD, Pehlivanoglu B, Memis B, Basturk O, et al. Pancreatic ductal adenocarcinomas associated with intraductal papillary mucinous neoplasms (IPMNs) versus pseudo-IPMNs: relative frequency, clinicopathologic characteristics and differential diagnosis. Mod Pathol. 2022; 35(1): 96-105. https://doi.org/10.1038/s41379-021-00902-x .
Bruner HC, Derksen PWB. Loss of E-cadherin-dependent cell–cell adhesion and the development and progression of cancer. Cold Spring Harb Perspect Biol. 2018; 10(3): a029330. https://doi.org/10.1101/cshperspect.a029330 .
Goodman SR. Goodman's Medical Cell Biology. 4th edition. Memphis: Academic Press. 2021. Chap 3. Cytoskeleton; p.57-100. https://doi.org/10.1016/B978-0-12-817927-7.00003-X
Jaiswal P, Yadav YK, Sinha SS, Singh MK. Expression of cytokeratin 8 in oral squamous cell cancer. Indian J Pathol Oncol. 2018; 5(1): 55-60. https://doi.org/10.18231/2394-6792.2018.0011
Wang S, Huang S, Sun YL. Epithelial-Mesenchymal Transition in Pancreatic Cancer: A Review. Biomed Res Int. 2017; 2017: 2646148-2646158. https://doi.org/10.1155/2017/2646148 .
Park HS, Han HJ, Lee S, Kim GM, Park S, Choi YA, et al. Detection of circulating tumor cells in breast cancer patients using cytokeratin-19 real-time RT-PCR. Yonsei Med J. 2017; 58(1): 19-26. https://doi.org/10.3349/ymj.2017.58.1.19 .
Sun DW, Zhang YY, Sun XD, Chen YG, Qiu W, Ji M, et al. Prognostic value of cytokeratin 19 in hepatocellular carcinoma: a meta-analysis. Clin Chim Acta. 2015; 25(448): 161-9. https://doi.org/10.1016/j.cca.2015.06.027 .
Battaglia RA, Delic S, Herrmann H, Snider NT. Vimentin on the move: new developments in cell migration. F1000Res. 2018; 7: 1796-10. https://doi.org/10.12688/f1000research.15967.1
Sharma P, Alsharif S, Fallatah A, Chung BM. Intermediate filaments as effectors of cancer development and metastasis: a focus on keratins, vimentin, and nestin. Cells. 2019; 8(5): 497-518. https://doi.org/10.3390/cells8050497 .
Strouhalova K, Přechová M, Gandalovičová A, Brábek J, Gregor M, Rosel D. Vimentin intermediate filaments as potential target for cancer treatment. Cancers. 2020; 12(1): 184. https://doi.org/10.3390/cancers12010184 .
Beardo P, Truan Cacho D, Izquierdo L, Alcover-Garcia JB, Alcaraz A, Extramiana J, et al. Cancer-specific survival stratification derived from tumor expression of tissue inhibitor of metalloproteinase-2 in non-metastatic renal cell carcinoma. Pathol Oncol Res. 2019; 25(1): 289-99. https://doi.org/10.1007/s12253-017-0339-7 .
Ismael MK. The Prognostic Value of some Epithelial-Mesenchymal Transition Markers and Metastasis-Related Markers in Human Transitional Cell Carcinoma of the Bladder. Baghdad Sci J. 2018;15(3):244-252. https://doi.org/10.21123/bsj.2018.15.3.0244
Pietrzak J, Szmajda-Krygier D, Wosiak A, Świechowski R, Michalska K, Mirowski M, et al. Changes in the expression of membrane type-matrix metalloproteinases genes (MMP14, MMP15, MMP16, MMP24) during treatment and their potential impact on the survival of patients with non-small cell lung cancer (NSCLC). Biomed Pharmacother. 2022; 146: 112559-112567. https://doi.org/10.1016/j.biopha.2021.112559
Fang Z, Liang W, Luo L. HSP27 promotes epithelial-mesenchymal transition through activation of the β-catenin/MMP3 pathway in pancreatic ductal adenocarcinoma cells. Transl Cancer Res. 2019; 8(4): 1268-1278. https://doi.org/10.21037/tcr.2019.07.13
Slapak EJ, Duitman J, Tekin C, Bijlsma MF, Spek CA. Matrix Metalloproteases in Pancreatic Ductal Adenocarcinoma: Key Drivers of Disease Progression?. Biology (Basel). 2020; 9(4): 80-101 https://doi.org/10.3390/biology9040080 .
Saw P .E, Song EW. Phage display screening of therapeutic peptide for cancer targeting and therapy. Protein Cell. 2019; 10(11): 787–807. https://doi.org/10.1007/s13238-019-0639-7
Pedrosa RM, Mustafa DA, Soffietti R, Kros JM. Breast cancer brain metastasis: molecular mechanisms and directions for treatment. Neuro Oncol. 2018; 20(11): 1439-49. https://doi.org/10.1093/neuonc/noy044
Raphael BJ, Hruban RH, Aguirre AJ, Moffitt RA, Yeh JJ, Stewart C, et al. Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma. Cancer Cell. 2017; 32(2): 185-203. https://doi.org/10.1016/j.ccell.2017.07.007
Steins A, Mackelenbergh MG van, Zalm AP van der, Klaassen R, Serrels B, Goris SG, et al. High-grade mesenchymal pancreatic ductal adenocarcinoma drives stromal deactivation through CSF-1. EMBO Rep. 2020; 21(5): e48780. https://doi.org/10.15252/embr.201948780 .
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