Suppression of some IncRNAs and Invasion by Boric Acid Treatment in Human Pancreatic Cancer

Yıl 2023, Cilt: 8 Sayı: 1, 108 - 114, 05.03.2023

Canan Eroğlu Güneş

https://doi.org/10.26453/otjhs.1200978

Öz

Objective: It was aimed to investigate the effects of boric acid on some lncRNAs and invasion in PANC-1 and MIA PaCa-2 pancreatic cancer cells.
Materials and Methods: The effects of boric acid on cell viability and invasion were investigated using XTT test and invasion chambers, respectively. lncRNA H19 and UCA1 expressions were evaluated in pancreatic cancer using TCGA data. Its effects on expressions of these lncRNAs and invasion genes were determined by qRT-PCR analysis.
Results: The IC50 doses of boric acid were calculated as 14.25 mM in PANC-1 cells and 15.71 mM in MIA PaCa-2. TCGA data showed that H19 and UCA1 expressions were elevated in pancreatic cancer. H19 and UCA1 lncRNA levels were decreased with boric acid treatment. In addition, boric acid increased CDH1 and TIMP1 in both cell lines. However, it suppressed CDH2 expression. Boric acid increased TIMP2 in PANC-1 cells and TIMP3 expression in MIA PaCa-2 cells. In the invasion test, boric acid significantly suppressed invasion in both cells.
Conclusions: Boric acid suppressed H19 and UCA1 expressions, which were found to be high in pancreatic cancer. In addition, it showed an anti-invasive effect by changing the expressions of genes that are important in invasion.

Anahtar Kelimeler

Boric acid, invasion, lncRNA-H19, lncRNA-UCA1, pancreatic cancer

Destekleyen Kurum

Scientific Research Projects of Necmettin Erbakan University

Proje Numarası

#221218018

İnsan Pankreas Kanserinde Borik Asit Uygulaması ile Bazı IncRNA’ların ve İnvazyonun Baskılanması

Öz

Amaç: Borik asidin bazı lncRNA'lar ve invazyon üzerine etkisinin PANC-1 ve MIA PaCa-2 pankreas kanseri hücrelerinde araştırılması amaçlanmıştır.
Materyal ve Metot: Borik asitin hücre canlılığı ve invazyon üzerine etkileri sırası ile XTT testi ve invazyon kuyucukları kullanılarak araştırılmıştır. TCGA verileri kullanılarak pankreas kanserinde lncRNA H19 ve UCA1 ifadeleri değerlendirilmiştir. Bu lncRNA’ların ve invazyon genlerinin ifadeleri üzerine etkileri qRT-PZR ile belirlenmiştir.
Bulgular: PANC-1 hücrelerinde borik asitin IC50 dozu 14.25 mM, MIA PaCa-2 de ise 15.71 mM olarak hesaplanmıştır. TCGA verileri H19 ve UCA1 ifadelerinin pankreas kanserinde yüksek olduğunu göstermiştir. Borik asit muamelesi ile H19 ve UCA1 lncRNA seviyeleri azalmıştır. Ayrıca borik asit iki hücre hattında CDH1 ve TIMP1 ifadesini arttırmıştır. CDH2 ifadesini baskılamıştır. Borik asit PANC-1 hücrelerinde TIMP2, MIA PaCa-2 hücrelerinde TIMP3 ifadesini arttırmıştır. İnvazyon testinde borik asit her iki hücrede invazyonu anlamlı derecede baskılanmıştır.
Sonuç: Borik asit pankreas kanserinde ifadesinin yüksek olduğu görülen H19 ve UCA1 ifadelerini baskılamıştır. Ayrıca invazyonda önemli olan genlerin ifadelerini değiştirerek anti-invaziv etki göstermiştir.

Anahtar Kelimeler

Borik asit, invazyon, lncRNA-H19, lncRNA-UCA1, pankreas kanseri

Proje Numarası

#221218018

Kaynakça

• 1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660
• 2. Korkmaz M, Uzgören E, Bakirdere S, Aydin F, Ataman OY. Effects of dietary boron on cervical cytopathology and on micronucleus frequency in exfoliated buccal cells. Environ Toxicol. 2007;22(1):17-25. doi:10.1002/tox.20229
• 3. Lang PA, Parkova A, Leissing TM, et al. Bicyclic boronates as potent inhibitors of AmpC, the class β-lactamase from Escherichia coli. Biomolecules. 2020;10(6):899. doi:10.3390/biom10060899
• 4. Maslah H, Skarbek C, Pethe S, Labruere R. Anticancer boron-containing prodrugs responsive to oxidative stress from the tumor microenvironment. Eur J Med Chem. 2020;207:112670. doi:10.1016/j.ejmech.2020.112670
• 5. Acaroz U, Ince S, Arslan-Acaroz D, et al. Bisphenol-A induced oxidative stress, inflammatory gene expression, and metabolic and histopathological changes in male Wistar albino rats: protective role of boron. Toxicol Res (Camb). 2019;8(2):262–269. doi:10.1039/c8tx00312b
• 6. Acerbo AS, Miller LM. Assessment of the chemical changes induced in human melanoma cells by boric acid treatment using infrared imaging. Analyst. 2009;134(8):1669-1674. doi:10.1039/b823234b
• 7. Di Renzo F, Cappelletti G, Broccia ML, Giavini E, Menegola E. Boric acid inhibits embryonic histone deacetylases: a suggested mechanism to explain boric acid-related teratogenicity. Toxicol Appl Pharmacol. 2007;220(2):178-185. doi:10.1016/j.taap.2007.01.001
• 8. Hung YH, Lin YC, Lin YT, et al. Suitability of boric acid as a boron drug for boron neutron capture therapy for hepatoma. Appl Radiat Isot. 2020;164:109254. doi:10.1016/j.apradiso.2020.109254
• 9. Sevimli M, Bayram D, Özgöçmen M, Armağan I, Semerci Sevimli T. Boric acid suppresses cell proliferation by TNF signaling pathway mediated apoptosis in SW-480 human colon cancer line. J Trace Elem Med Biol. 2022;71:126958. doi:10.1016/j.jtemb.2022.126958
• 10. Gallardo-Williams MT, Chapin RE, King PE, et al. Boron supplementation inhibits the growth and local expression of IGF-1 in human prostate adenocarcinoma (LNCap) tumors in nude mice. Toxicol Pathol. 2004;32(1):73-78. doi:10.1080/01926230490260899
• 11. Gibb EA, Brown CJ, Lam WL. The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 2011;10: 38. doi:10.1186/1476-4598-10-38
• 12. Raveh E, Matouk I, Gilon M, et al. The H19 long non-coding RNA in cancer initiation, progression and metastasis-A proposed unifying theory. Mol Cancer. 2015;14:184. doi:10.1186/s12943-015-0458-2
• 13. Matouk IJ, Raveh E, Abu-lail R, et al. Oncofetal H19 RNA promotes tumor metastasis. Biochimica et Biophysica Acta. 2014;1843(7):1414-1426. doi:10.1016/j.bbamcr. 2014.03.023
• 14. Sun Y, Zhu Q, Yang W, et al. LncRNA H19/MiR-194/PFTK1 axis modulates the cell proliferation and migration of pancreatic cancer. J Cell Biochem. 2019;120(3):3874–3886. doi:10.1002/jcb.27669
• 15. Xue M, Chen W, Li X. Urothelial cancer associated 1: A long noncoding RNA with a crucial role in cancer. J Cancer Res Clin Oncol. 2016;142(7):1407–1419. doi:10.1007/s00432-015-2042-y
• 16. Chen P, Wan D, Zheng D, Zheng Q, Wu F, Zhi Q. Long non-coding RNA UCA1 promotes the tumorigenesis in pancreatic cancer. BioMed Pharmacother. 2016;83:1220–1226. doi:10.1016/j.biopha.2016.08.041
• 17. Hay ED, Zuk A. Transformations between epithelium and mesenchyme: normal, pathological, and experimentally induced. Am J Kidney Dis. 1995;26(4): 678–690. doi:10.1016/0272-6386(95)90610-x
• 18. Bourboulia D, Stetler-Stevenson WG. Matrix metalloProteinases (MMPS) and tissue inhibitors of metalloproteinases (TIMPs): positive and negative regulators in tumor cell adhesion. Semin Cancer Biol. 2010;20(3):161-168. doi:10.1016/j.semcancer. 2010.05.002
• 19. Eroğlu Güneş C. Boric acid shows ER stress and apoptosis mediated anticancer activity in human pancreatic cancer MIA PaCa-2 and PANC-1 cells. Selcuk Med J. 2023; 39(1):1-6.
• 20. Dodurga Y, Seçme M, Eroğlu C, et al. Investigation of the effects of a sulfite molecule on human neuroblastoma cells via a novel oncogene URG4/URGCP. Life Sci. 2015;143:27-34. doi:10.1016/j.lfs.2015.10.005
• 21. Eroğlu-Güneş C, Güçlü E, Vural H, Kurar E. Knockdown of lncRNA ZEB2NAT suppresses epithelial mesenchymal transition, metastasis and proliferation in breast cancer cells. Gene. 2021; 805:145904. doi:10.1016/j.gene.2021.145904
• 22. Cebeci E, Yüksel B, Şahin F. Anti-cancer effect of boron derivatives on small-cell lung cancer. J Trace Elem Med Biol. 2022;70:126923. doi:10.1016/j.jtemb.2022.126923
• 23. Turkez H, Arslan ME, Tatar A, Mardinoglu A. Promising potential of boron compounds against glioblastoma: In vitro antioxidant, anti-inflammatory and anticancer studies. Neurochem Int. 2021;149:105137. doi:10.1016/j.neuint.2021.105137
• 24. Özyarım ŞC, Karabağ Çoban F. Investigation of the apoptotic and antiproliferative effects of boron on CCL-233 human colon cancer cells. Cell J. 2021;23(4):429-434. doi:10.22074/cellj.2021.7259
• 25. El-Hefny IM, Al Senosy NK, Hozayen WG, Ahmed AE, Diab A, Basal WT. Evaluation of the cytotoxicity and apoptotic induction in human liver cell lines exposed to three food additives. Recent Pat Food Nutr Agric. 2020;11(3):193-201. doi:10.2174/2212798411666200217124630
• 26. Barranco WT, Eckhert CD. Cellular changes in boric acid-treated DU-145 prostate cancer cells. Br J Cancer. 2006;94(6):884-890. doi:10.1038/sj.bjc.6603009
• 27. Xiong G, Pan S, Jin J, et al. Long noncoding competing endogenous RNA networks in pancreatic cancer. Front Oncol. 2021;11:765216. doi:10.3389/fonc.2021.765216
• 28. Ma C, Nong K, Zhu H, et al. H19 promotes pancreatic cancer metastasis by depressing let-7’s suppression on its target HMGA2- mediated EMT. Tumour Biol. 2014;35(9):9163-9169. doi:10.1007/s13277-014-2185-5
• 29. Guo Z, Wang X, Yang Y, et al. Hypoxic tumor-derived exosomal long noncoding RNA UCA1 promotes angiogenesis via MiR-96-5p/AMOTL2 in pancreatic cancer. Mol Ther Nucleic Acids. 2020;22:179–95. doi:10.1016/j.omtn.2020.08.021
• 30. Zhou Y, Chen Y, Ding W, et al. LncRNA UCA1 impacts cell proliferation, invasion, and migration of pancreatic cancer through regulating MiR-96/FOXO3. IUBMB Life. 2018;70(4):276–290. doi:10.1002/iub.1699