Research Article
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How do the effective therapeutics for hepatocellular carcinoma treatment change PIWI Interacting RNA expressions?

Year 2020, Volume 4, Issue 3, 242 - 246, 29.10.2020
https://doi.org/10.30565/medalanya.755050

Abstract

Aim: PIWI interacting RNAs (piRNAs) are novel members of small non-coding RNAs that cannot produce proteins but are effective on transcription and post-transcriptional mechanisms of cells. Nowadays, the application of both natural compounds and vitamins is essential for treatment of cancer cells instead of chemical compounds. In this study, we aimed to detect possible expression changes of piRNAs in order to compare 4- Hydroxycoumarin to the active form of vitamin D (1.25-Dihydroxyvitamin D) in hepatocellular carcinoma.

Methods: According to our previous study, HePG2 cells were treated with 4- Hydroxycoumarin, 1.25-Dihydroxyvitamin D and drug form of vitamin D at the optimal time and concentration. After treatment, the total RNA was isolated and expressions of piR-Hep-1 and piR-651 were determined by using Real Time Polymerase Chain Reactions.

Results: According to our obtained data, statistically significant upregulation of piR-651 expression was observed in 4-Hydroxycoumarin-treated HePG2 cells compared to control (p<0.001). However, the expression of piR-Hep-1 statistically was not affected from 4- Hydroxycoumarin treatment (p>0.05). In contrast, 1.25-dihydroxyvitamin treatment downregulated the expression of piR-Hep-1 statistically significant in HePG2 cells (p<0.001). piR-Hep-1 was not statistically significant effected from drug form of vitamin D treatment (p>0.05).

Conlusion: Our results indicated that some of the piRNAs might have special expression patterns in hepatocellular carcinoma and these expression patterns can be regulated by treated natural compounds. We suggest that substances that are observed to be effective in hepatocellular carcinoma individually may result in different piRNA expression changes contrary to the expectations.

References

  • 1. Ng KW, Anderson C, Marshall EA, Minatel BC, Enfield KS, Saprunoff HL, et al. Piwi- interacting RNAs in cancer: emerging functions and clinical utility. Mol Cancer. 2016; 15: p. 5 doi: 10.1186/s12943-016-0491-9.
  • 2. Cui L, Lou Y, Zhang X, Zhou H, Deng H, Song H, et al. Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using piRNAs as markers. Clin Biochem. 2011; 44(13): p. 1050-7 doi: 10.1016/j.clinbiochem.2011.06.004.
  • 3. Öner Ç. Two different mechanisms of two different non-coding RNAs—MicroRNAs and PIWI-interacting RNAs: From origin to cancer. 2019: p. 3-34 doi: 10.1016/b978-0- 12-815669-8.00001-4.
  • 4. Law PT, Qin H, Ching AK, Lai KP, Co NN, He M, et al. Deep sequencing of small RNA transcriptome reveals novel non-coding RNAs in hepatocellular carcinoma. J Hepatol. 2013; 58(6): p. 1165-73 doi: 10.1016/j.jhep.2013.01.032.
  • 5. Sasaki T, Shiohama A, Minoshima S, and Shimizu N. Identification of eight members of the Argonaute family in the human genome. Genomics. 2003; 82(3): p. 323-30.
  • 6. Muller S, Raulefs S, Bruns P, Afonso-Grunz F, Plotner A, Thermann R, et al. Next- generation sequencing reveals novel differentially regulated mRNAs, lncRNAs, miRNAs, sdRNAs and a piRNA in pancreatic cancer. Mol Cancer. 2015; 14: p. 94 doi: 10.1186/s12943-015-0358-5.
  • 7. He W, Wang Z, Wang Q, Fan Q, Shou C, Wang J, et al. Expression of HIWI in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis. BMC Cancer. 2009; 9(426).
  • 8. Cheng J, Guo JM, Xiao BX, Miao Y, Jiang Z, Zhou H, et al. piRNA, the new non- coding RNA, is aberrantly expressed in human cancer cells. Clinica Chimica Acta. 2011; 412(17-18): p. 1621-1625 doi: 10.1016/j.cca.2011.05.015.
  • 9. Matsuda T and Saika K. Trends in liver cancer mortality rates in Japan, USA, UK, France and Korea based on the WHO mortality database. Jpn J Clin Oncol. . 2012; 42: p. 360-1.
  • 10. Masuda S, Byford V, Kremer R, Makin HL, Kubodera N, Nishii Y, et al. In vitro metabolism of the vitamin D analog, 22-oxacalcitriol, using cultured osteosarcoma, hepatoma, and keratinocyte cell lines. J Biol Chem. 1996; 271(15): p. 8700-8 doi: 10.1074/jbc.271.15.8700.
  • 11. Elangovan H, Chahal S, and Gunton JE. Vitamin D in liver disease: Current evidence and potential directions. Biochim Biophys Acta Mol Basis Dis. 2017; 1863(4): p. 907- 916 doi: 10.1016/j.bbadis.2017.01.001.
  • 12. Knowles BB, Howe CC, and Aden DP. Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science. 1980; 209(4455): p. 497-9 doi: 10.1126/science.6248960.
  • 13. Abraham K, Wohrlin F, Lindtner O, Heinemeyer G, and Lampen A. Toxicology and risk assessment of coumarin: focus on human data. Mol Nutr Food Res. 2010; 54(2): p. 228-39 doi: 10.1002/mnfr.200900281.
  • 14. Rennenberg RJ, van Varik BJ, Schurgers LJ, Hamulyak K, Ten Cate H, Leiner T, et al. Chronic coumarin treatment is associated with increased extracoronary arterial calcification in humans. Blood. 2010; 115(24): p. 5121-3 doi: 10.1182/blood-2010-01- 264598.
  • 15. Marshall ME, Butler K, and Fried A. Phase I evaluation of coumarin (1,2- benzopyrone) and cimetidine in patients with advanced malignancies. Mol Biother. 1991;3(3):170-8.
  • 16. JL M, LG G, ED C, LM G, CD Z, and WR F. Phase II evaluation of coumarin (1,2- benzopyrone) in metastatic prostatic carcinoma. Prostate. 1992; 20(2): p. 123-31.
  • 17. Öner Ç, İSan H, AktaŞ RG, and ÇOlak E. Vİtamİn D’nİn HepatoselÜler Karsİnom Üzerİndekİ Etkİsİ. Osmangazİ Journal of Medicine. 2019doi: 10.20515/otd.584749.
  • 18. Siddiqi S and Matushansky I. Piwis and piwi-interacting RNAs in the epigenetics of cancer. J Cell Biochem. 2012; 113(2): p. 373-80 doi: 10.1002/jcb.23363.
  • 19. Wahle KWJ, Brown I, Rotondo D, and Heys SD, Plant Phenolics in the Prevention and Treatment of Cancer, in Bio-Farms for Nutraceuticals: Functional Food and Safety Control by Biosensors, M.T. Giardi, G. Rea, and B. Berra, Editors. 2010, Springer US: Boston, MA. p. 36-51.
  • 20. Clere N, Faure S, Martinez MC, and Andriantsitohaina R. Anticancer properties of flavonoids: roles in various stages of carcinogenesis. Cardiovasc Hematol Agents Med Chem. 2011; 9(2): p. 62-77 doi: 10.2174/187152511796196498.
  • 21. Egan D, James P, Cooke D, and O'Kennedy R. Studies on the cytostatic and cytotoxic effects and mode of action of 8-nitro-7-hydroxycoumarin. Cancer Letters. 1997; 118(2): p. 201-211 doi: 10.1016/s0304-3835(97)00331-5.
  • 22. Stefanova TH, Nikolova NJ, Toshkova RA, and Neychev HO. Antitumor and immunomodulatory effect of coumarin and 7-hydroxycoumarin against Sarcoma 180 in mice. J Exp Ther Oncol. 2007; 6(2): p. 107-15.
  • 23. Finn GJ, Creaven B, and Egan DA. Study of the in vitro cytotoxic potential of natural and synthetic coumarin derivatives using human normal and neoplastic skin cell lines. Melanoma Res. 2001; 11(5): p. 461-7 doi: 10.1097/00008390-200110000-00004.
  • 24. Pourgholami MH, Akhter J, Lu Y, and Morris DL. In vitro and in vivo inhibition of liver cancer cells by 1,25-dihydroxyvitamin D3. Cancer Letters. 2000; 151(1): p. 97-102 doi: 10.1016/s0304-3835(99)00416-4.
  • 25. Huang J, Yang G, Huang Y, and Zhang S. 1,25(OH)2D3 induced apoptosis of human hepatocellular carcinoma cells in vitro and inhibited their growth in a nude mouse xenograft model by regulating histone deacetylase 2. Biochimie. 2018; 146: p. 28-34 doi: 10.1016/j.biochi.2017.11.012.

Hepatoselüler karsinom tedavisi için etkili terapötikler PIWI Interacting RNA ifadelerini nasıl değiştirir?

Year 2020, Volume 4, Issue 3, 242 - 246, 29.10.2020
https://doi.org/10.30565/medalanya.755050

Abstract

Amaç: PIWI interacting RNA’lar (piRNA’lar) herhangi bir protein üretemeyen ancak hücrelerin transkripsiyon ve transkripsiyon sonrası mekanizmalarında etkili olan küçük kodlayıcı olmayan RNA'ların yeni üyeleridir. Günümüzde, kanser hücrelerinin tedavisinde kimyasal bileşikler yerine, hem doğal bileşikler hem de vitaminler uygulanabilirliği araştırılmaktadır. Bu çalışmadaki amacımız, 4-Hidroksikoumarinin ve aktif D vitamini formunun (1.25-dihidroksivitamin D) hepatoselüler karsinomada piRNA'ların olası ekspresyonları üzerindeki değişiklikleri belirlemektir.

Yöntemler: Önceki çalışmamızdan elde edilen verilere göre, optimal zaman ve konsantrasyonu belirlenen 4-Hidroksikoumarin, 1.25-dihidroksivitamin D ve D vitamininin ilaç formu HePG2 hücrelerine uygulandı. Uygulamadan sonra total RNA izole edildi. piR-Hep-1 ve piR-651'in ekspresyonları Gerçek Zamanlı Polimeraz Zincir Reaksiyonları kullanılarak belirlendi.

Bulgular: Elde edilen verilere göre, 4-Hidroksikoumarin uygulanan HePG2 hücrelerinde kontrole göre piR-651 ekspresyonunda istatistiksel olarak anlamlı bir artış gözlenmiştir (p< 0.001). Bununla birlikte, 4-Hidroksikoumarin uygulamasından sonra piR-Hep-1 ekspresyonundaki değişim istatistiksel olarak anlamlı değildir (p> 0.05). Buna karşılık, 1,25- dihidroksivitamin uygulaması HePG2 hücrelerinde piR-Hep-1 ekspresyonunu istatistiksel olarak anlamlı şekilde azaltmıştır (p <0.001). D vitamininin ilaç formunun uygulamasından sonra piR-Hep-1 ekspresyonundaki azalma istatistiksel olarak anlamlı değildir (p> 0.05).

Sonuç: Tüm bu veriler, piRNA'ların bazılarının hepatoselüler karsinomda özel ekspresyon paternlerine sahip olabileceğini ve bu ekspresyon paternlerinin, uygulanan doğal bileşikler tarafından düzenlenebileceğini göstermektedir. Hepatoselüler karsinomda tek tek etkili olduğu gözlenen maddelerin, beklentilerin aksine farklı piRNA ekspresyon değişikliklerine neden olabileceğini savunmaktayız.

References

  • 1. Ng KW, Anderson C, Marshall EA, Minatel BC, Enfield KS, Saprunoff HL, et al. Piwi- interacting RNAs in cancer: emerging functions and clinical utility. Mol Cancer. 2016; 15: p. 5 doi: 10.1186/s12943-016-0491-9.
  • 2. Cui L, Lou Y, Zhang X, Zhou H, Deng H, Song H, et al. Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using piRNAs as markers. Clin Biochem. 2011; 44(13): p. 1050-7 doi: 10.1016/j.clinbiochem.2011.06.004.
  • 3. Öner Ç. Two different mechanisms of two different non-coding RNAs—MicroRNAs and PIWI-interacting RNAs: From origin to cancer. 2019: p. 3-34 doi: 10.1016/b978-0- 12-815669-8.00001-4.
  • 4. Law PT, Qin H, Ching AK, Lai KP, Co NN, He M, et al. Deep sequencing of small RNA transcriptome reveals novel non-coding RNAs in hepatocellular carcinoma. J Hepatol. 2013; 58(6): p. 1165-73 doi: 10.1016/j.jhep.2013.01.032.
  • 5. Sasaki T, Shiohama A, Minoshima S, and Shimizu N. Identification of eight members of the Argonaute family in the human genome. Genomics. 2003; 82(3): p. 323-30.
  • 6. Muller S, Raulefs S, Bruns P, Afonso-Grunz F, Plotner A, Thermann R, et al. Next- generation sequencing reveals novel differentially regulated mRNAs, lncRNAs, miRNAs, sdRNAs and a piRNA in pancreatic cancer. Mol Cancer. 2015; 14: p. 94 doi: 10.1186/s12943-015-0358-5.
  • 7. He W, Wang Z, Wang Q, Fan Q, Shou C, Wang J, et al. Expression of HIWI in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis. BMC Cancer. 2009; 9(426).
  • 8. Cheng J, Guo JM, Xiao BX, Miao Y, Jiang Z, Zhou H, et al. piRNA, the new non- coding RNA, is aberrantly expressed in human cancer cells. Clinica Chimica Acta. 2011; 412(17-18): p. 1621-1625 doi: 10.1016/j.cca.2011.05.015.
  • 9. Matsuda T and Saika K. Trends in liver cancer mortality rates in Japan, USA, UK, France and Korea based on the WHO mortality database. Jpn J Clin Oncol. . 2012; 42: p. 360-1.
  • 10. Masuda S, Byford V, Kremer R, Makin HL, Kubodera N, Nishii Y, et al. In vitro metabolism of the vitamin D analog, 22-oxacalcitriol, using cultured osteosarcoma, hepatoma, and keratinocyte cell lines. J Biol Chem. 1996; 271(15): p. 8700-8 doi: 10.1074/jbc.271.15.8700.
  • 11. Elangovan H, Chahal S, and Gunton JE. Vitamin D in liver disease: Current evidence and potential directions. Biochim Biophys Acta Mol Basis Dis. 2017; 1863(4): p. 907- 916 doi: 10.1016/j.bbadis.2017.01.001.
  • 12. Knowles BB, Howe CC, and Aden DP. Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science. 1980; 209(4455): p. 497-9 doi: 10.1126/science.6248960.
  • 13. Abraham K, Wohrlin F, Lindtner O, Heinemeyer G, and Lampen A. Toxicology and risk assessment of coumarin: focus on human data. Mol Nutr Food Res. 2010; 54(2): p. 228-39 doi: 10.1002/mnfr.200900281.
  • 14. Rennenberg RJ, van Varik BJ, Schurgers LJ, Hamulyak K, Ten Cate H, Leiner T, et al. Chronic coumarin treatment is associated with increased extracoronary arterial calcification in humans. Blood. 2010; 115(24): p. 5121-3 doi: 10.1182/blood-2010-01- 264598.
  • 15. Marshall ME, Butler K, and Fried A. Phase I evaluation of coumarin (1,2- benzopyrone) and cimetidine in patients with advanced malignancies. Mol Biother. 1991;3(3):170-8.
  • 16. JL M, LG G, ED C, LM G, CD Z, and WR F. Phase II evaluation of coumarin (1,2- benzopyrone) in metastatic prostatic carcinoma. Prostate. 1992; 20(2): p. 123-31.
  • 17. Öner Ç, İSan H, AktaŞ RG, and ÇOlak E. Vİtamİn D’nİn HepatoselÜler Karsİnom Üzerİndekİ Etkİsİ. Osmangazİ Journal of Medicine. 2019doi: 10.20515/otd.584749.
  • 18. Siddiqi S and Matushansky I. Piwis and piwi-interacting RNAs in the epigenetics of cancer. J Cell Biochem. 2012; 113(2): p. 373-80 doi: 10.1002/jcb.23363.
  • 19. Wahle KWJ, Brown I, Rotondo D, and Heys SD, Plant Phenolics in the Prevention and Treatment of Cancer, in Bio-Farms for Nutraceuticals: Functional Food and Safety Control by Biosensors, M.T. Giardi, G. Rea, and B. Berra, Editors. 2010, Springer US: Boston, MA. p. 36-51.
  • 20. Clere N, Faure S, Martinez MC, and Andriantsitohaina R. Anticancer properties of flavonoids: roles in various stages of carcinogenesis. Cardiovasc Hematol Agents Med Chem. 2011; 9(2): p. 62-77 doi: 10.2174/187152511796196498.
  • 21. Egan D, James P, Cooke D, and O'Kennedy R. Studies on the cytostatic and cytotoxic effects and mode of action of 8-nitro-7-hydroxycoumarin. Cancer Letters. 1997; 118(2): p. 201-211 doi: 10.1016/s0304-3835(97)00331-5.
  • 22. Stefanova TH, Nikolova NJ, Toshkova RA, and Neychev HO. Antitumor and immunomodulatory effect of coumarin and 7-hydroxycoumarin against Sarcoma 180 in mice. J Exp Ther Oncol. 2007; 6(2): p. 107-15.
  • 23. Finn GJ, Creaven B, and Egan DA. Study of the in vitro cytotoxic potential of natural and synthetic coumarin derivatives using human normal and neoplastic skin cell lines. Melanoma Res. 2001; 11(5): p. 461-7 doi: 10.1097/00008390-200110000-00004.
  • 24. Pourgholami MH, Akhter J, Lu Y, and Morris DL. In vitro and in vivo inhibition of liver cancer cells by 1,25-dihydroxyvitamin D3. Cancer Letters. 2000; 151(1): p. 97-102 doi: 10.1016/s0304-3835(99)00416-4.
  • 25. Huang J, Yang G, Huang Y, and Zhang S. 1,25(OH)2D3 induced apoptosis of human hepatocellular carcinoma cells in vitro and inhibited their growth in a nude mouse xenograft model by regulating histone deacetylase 2. Biochimie. 2018; 146: p. 28-34 doi: 10.1016/j.biochi.2017.11.012.

Details

Primary Language English
Subjects Medicine
Journal Section Research Article
Authors

Çağrı ÖNER (Primary Author)
Maltepe University, Medical Faculty, Department of Medical Biology and Genetics, 34857, İstanbul/TURKEY
0000-0003-3771-3277
Türkiye


Necdet ALTINER This is me
Maltepe University, Medical Faculty, Department of Histology and Embryology, 34857, İstanbul/TURKEY
0000-0000-0000-0000
Türkiye


Ertugrul COLAK
Eskişehir Osmangazi University, Medical Faculty, Department of Biostatistics, 26040, Eskişehir/TURKEY
0000-0003-3251-1043
Türkiye

Publication Date October 29, 2020
Application Date June 20, 2020
Acceptance Date September 25, 2020
Published in Issue Year 2020, Volume 4, Issue 3

Cite

Vancouver Öner Ç. , Altıner N. , Colak E. How do the effective therapeutics for hepatocellular carcinoma treatment change PIWI Interacting RNA expressions?. Acta Medica Alanya. 2020; 4(3): 242-246.

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