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Kolorektal kanserde lncRNA DPP10-AS1 ekspresyonu tümör baskılayıcı ve tümör mikroçevresinde metabolit transportuyla ilişkili olabilir mi?

Yıl 2020, Cilt: 20 Sayı: 3, 162 - 168, 11.01.2022
https://doi.org/10.17941/agd.974118

Öz

Giriş ve amaç: Onkogen ve tümör baskılayıcı gen ifadeleri başta olmak üzere birçok RNA ve proteinle moleküler etkileşimde bulunabilen lncRNA’lar solid organ kanserlerinde ilişkilendirilmeye başlanmıştır. Deneysel çalışmalarda Wnt/β -katenin yolağı ile ilişkilendirilen lncRNA DPP10-AS1’in çalışmamızda kolorektal tümörlerdeki ifadesi ve serum biyobelirteçleriyle olan ilişkisinin incelenmesi amaçlanmıştır.
Gereç ve yöntem: Kolorektal kanser tanılı elli bir olgunun tümör ve tümörsüz çevre dokusuna ait formalinle fikse edilmiş parafine emdirilmiş bloklarından total RNA izolasyonu gerçekleştirildi. İzole edilen total RNA’dan lncRNA’lara spesifik c-DNA sentezi gerçekleştirildikten sonra DPP10-AS1’e özgü primerler ile gerçek zamanlı polimeraz zincir reaksiyonu ile ekspresyon düzeyi tespit edildi. Ekspresyon düzeyleri olguların serum biyomarkerlarıyla korelasyon yönünden incelendi.
Bulgular: lncRNA DPP10-AS1 ‘in katlı değişimi tümörsüz çevre dokusunda tümör dokusuna göre yaklaşık 5,7 kat yüksek olduğu tespit edilmiştir (P=0,0002). Histopatolojik bulgularla lncRNA DPP10-AS1 arasında istatistiksel bir farklılık tespit edilmezken, uzak organ metastazı olmayanlarda olanlara göre 1,5 kat yüksek olduğu izlenmiştir (p>0.05). DPP10-AS1 ile albümin (r: ,403; p=0,033) ve amilaz (r: ,450; p= 0,031) arasında pozitif korelasyonları tespit edildi.
Sonuç: DPP10-AS1’in tümör baskılayıcı rolü olduğunu, albüminle korelasyonu tümör mikroçevresinde sekonder metabolitlerin transportunda rol oynayabileceğini düşündürmektedir. DPP10-AS1 ile amilaz korelasyonunun literatürde tanımlanan yüksek amilaz düzeylerinin tümör farklılaşması, çoğalması sürecindeki etkisiyle paralele şekilde tümör mikroçevresinin bir yanıtı olarak ifade edilebileceğini düşünmekteyiz.

Destekleyen Kurum

Gaziantep Üniversitesi Bilimsel Araştırmalar Proje Birimi

Proje Numarası

TF.ALT.19.19

Kaynakça

  • 1. Kuipers EJ, Grady WM, Lieberman D, et al. Colorectal cancer. Nat Rev Dis Primers 2015; 1:15065.
  • 2. Mármol I, Sánchez-de-Diego C, Pradilla Dieste A, et al. Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer. Int J Mol Sci. 2017;18(1):197.
  • 3. Zhang J, Zhang A, Wang Y, et al. New insights into the roles of ncRNA in the STAT3 pathway. Future Oncol 2012; 8:723-730.
  • 4. Liao XH, Wang JG, et al. Long intergenic non-coding RNA APOC1P1-3 inhibits apoptosis by decreasing alpha-tubulin acetylation in breast cancer. Cell death & disease 2016; 7: e2236.
  • 5. Yuan JH, Yang F, Wang F, et al. A long noncoding RNA activated by TGF-beta promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer cell 2014;25(5):666-81.
  • 6. Hamilton MJ, Young MD, Sauer S, et al. The interplay of long non-coding RNAs and MYC in cancer. AIMS Biophys 2015;2(4):794-809.
  • 7. Gibb EA, Brown CJ, Lam WL. The functional role of long non-coding RNA in human carcinomas. Mol Cancer 2011;10:38.
  • 8. Tian H, Pan J, Fang S, et al. Epigenetic regulation contributes to the oncogenic role of DPP10-AS1 in lung cancer. SSRN 2019;3421596.
  • 9. Liu G, Zhao H, Song Q, et al. Long non-coding RNA DPP10-AS1 exerts anti-tumor effects on colon cancer via the upregulation of ADCY1 by regulating microRNA-127-3p. Aging (Albany NY) 2021;13(7):9748-9765.
  • 10. Polakis P. Wnt signaling in cancer. Cold Spring Harb Perspect Biol. 2012;4(5):a008052.
  • 11. Li F, Chong ZZ, Maiese K. Winding through the WNT pathway during cellular development and demise. Histol Histopathol 2006;21(1):103-124.
  • 12. Polakis P. Wnt signaling and cancer. Genes Dev 2000;14(15):1837-51.
  • 13. Kikuchi A. Regulation of beta-catenin signaling in the Wnt pathway. Biochem Biophys Res Commun 2000;268(2):243-8.
  • 14. Giles RH, van Es JH, Clevers H. Caught up in a Wnt storm: Wnt signaling in cancer. Biochim Biophys Acta 2003 Jun 5;1653(1):1-24.
  • 15. Lin J, Tan X, Qiu L, et al. Long Noncoding RNA BC032913 as a Novel Therapeutic Target for Colorectal Cancer that Suppresses Metastasis by Upregulating TIMP3. Mol Ther Nucleic Acids 2017;8:469-481.
  • 16. Ballantyne MD, McDonald RA, Baker AH. lncRNA/MicroRNA interactions in the vasculature. Clin Pharmacol Ther 2016;99(5):494-501.
  • 17. McMillan DC, Canna K, McArdle CS. Systemic inflammatoryresponse predicts survival following curative resection of col-orectal cancer. Br J Surg 2003;90:215-9.
  • 18. Skinner AC, Steiner MJ, Henderson FW, et al. Multiple markers of inflammation and weight status: cross-sectional analyses throughout childhood. Pediatrics. 2010; 125(4):e801-9.
  • 19. Fox P, Hudson M, Brown C, et al. Markers of systemic inflammation predict survival in patients with advanced renal cell cancer. Br J Cancer. 2013;109(1):147-53.
  • 20. Dai M, Chen X, Mo S, et al. Meta-signature LncRNAs serve as novel biomarkers for colorectal cancer: integrated bioinformatics analysis, experimental validation and diagnostic evaluation. Sci Rep 2017;7:46572.
  • 21. Arun G, Diermeier SD, Spector DL. Therapeutic Targeting of Long Non-Coding RNAs in Cancer. Trends Mol Med 2018;3:257-277.
  • 22. Qi SY, Riviere PJ, Trojnar J, et al. Cloning and characterization of dipeptidyl peptidase 10, a new member of an emerging subgroup of serine proteases. Biochem J 2003;373(Pt 1):179-89.
  • 23. Allen M, Heinzmann A, Noguchi E, et al. Positional cloning of a novel gene influencing asthma from chromosome 2q14. Nat Genet 2003;35:258-63.
  • 24. Park HS, Yeo HY, Chang HJ, et al. Dipeptidyl peptidase 10, a novel prognostic marker in colorectal cancer. Yonsei Med J 2013;54(6):1362-9.
  • 25. Gupta D, Lis CG. Pretreatment serum albumin as a predictor of cancer survival: a systematic review of the epidemiological literature. Nutr J 2010;9:69.
  • 26. Lu X, Guo W, Xu W, et al. Prognostic value of the Glasgow prognostic score in colorectal cancer: a meta-analysis of 9,839 patients. Cancer Manag Res. 2018;11:229-249.
  • 27. Shibutani M, Maeda K, Nagahara H, et al. The significance of the C-reactive protein to albumin ratio as a marker for predicting survival and monitoring chemotherapeutic effectiveness in patients with unresectable metastatic colorectal cancer. Springerplus 2016;5(1):1798.
  • 28. Tominaga T, Nonaka T, Sumida Yet al. The C-Reactive Protein to Albumin Ratio as a Predictor of Severe Side Effects of Adjuvant Chemotherapy in Stage III Colorectal Cancer Patients. PLoS One 2016;11(12):e0167967.
  • 29. Belau F, Metzner K, Christ T, et al. DPP10 is a new regulator of Nav1.5 channels in human heart. Int J Cardiol 2019;284:68-73.
  • 30. Roch AM, Parikh JA, Al-Haddad MA, et al. Abnormal serum pancreatic enzymes, but not pancreatitis, are associated with an increased risk of malignancy in patients with intraductal papillary mucinous neoplasms. Surgery. 2014;156(4):923-9.
  • 31. Date K, Yamazaki T, Toyoda Y, et al. α-Amylase expressed in human small intestinal epithelial cells is essential for cell proliferation and differentiation. J Cell Biochem 2020;121(2):1238-1249.

Could lncRNA DPP10-AS1 expression in colorectal cancer be associated with tumor suppressor and metabolite transport in the tumor microenvironment?

Yıl 2020, Cilt: 20 Sayı: 3, 162 - 168, 11.01.2022
https://doi.org/10.17941/agd.974118

Öz

Background and aims: lncRNAs, which can interact with many RNAs and proteins, especially oncogene and tumor suppressor gene expressions, have begun to be associated in solid organ cancers. We aimed to examine the expression of lncRNA DPP10-AS1, which is associated with the Wnt/β-catenin pathway in experimental studies, in colorectal tumors and its relationship with serum biomarkers.
Materials and methods: Total RNA isolation was performed from formalin-fixed paraffin-impregnated blocks of tumor and tumor-free surrounding tissue of fifty-one patients with colorectal cancer. After specific c-DNA synthesis was performed from the isolated total RNA to lncRNAs, the expression level was determined by real-time polymerase chain reaction with primers specific to DPP10-AS1. Expression levels were analyzed in terms of correlation with serum biomarkers of the cases.
Results: The fold change of lncRNA DPP10-AS1 was found to be approximately 5.7 times higher in tumor-free surrounding tissue than in tumor tissue (P=0.0002). While no statistical difference was detected between histopathological findings and lncRNA DPP10-AS1, it was observed that it was 1.5 times higher in patients without distant organ metastasis (p>0.05). Positive correlations were detected between DPP10-AS1 and albumin (r: .403; p=0.033) and amylase (r: .450; p= 0.031).
Conclusion: DPP10-AS1 has a tumor suppressive role, and its correlation with albumin suggests that it may play a role in the transport of secondary metabolites in the tumor microenvironment. We think that the correlation between DPP10-AS1 and amylase can be expressed as a response of the tumor microenvironment in parallel with the effect of high amylase levels on tumor differentiation and proliferation, as defined in the literature.

Proje Numarası

TF.ALT.19.19

Kaynakça

  • 1. Kuipers EJ, Grady WM, Lieberman D, et al. Colorectal cancer. Nat Rev Dis Primers 2015; 1:15065.
  • 2. Mármol I, Sánchez-de-Diego C, Pradilla Dieste A, et al. Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer. Int J Mol Sci. 2017;18(1):197.
  • 3. Zhang J, Zhang A, Wang Y, et al. New insights into the roles of ncRNA in the STAT3 pathway. Future Oncol 2012; 8:723-730.
  • 4. Liao XH, Wang JG, et al. Long intergenic non-coding RNA APOC1P1-3 inhibits apoptosis by decreasing alpha-tubulin acetylation in breast cancer. Cell death & disease 2016; 7: e2236.
  • 5. Yuan JH, Yang F, Wang F, et al. A long noncoding RNA activated by TGF-beta promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer cell 2014;25(5):666-81.
  • 6. Hamilton MJ, Young MD, Sauer S, et al. The interplay of long non-coding RNAs and MYC in cancer. AIMS Biophys 2015;2(4):794-809.
  • 7. Gibb EA, Brown CJ, Lam WL. The functional role of long non-coding RNA in human carcinomas. Mol Cancer 2011;10:38.
  • 8. Tian H, Pan J, Fang S, et al. Epigenetic regulation contributes to the oncogenic role of DPP10-AS1 in lung cancer. SSRN 2019;3421596.
  • 9. Liu G, Zhao H, Song Q, et al. Long non-coding RNA DPP10-AS1 exerts anti-tumor effects on colon cancer via the upregulation of ADCY1 by regulating microRNA-127-3p. Aging (Albany NY) 2021;13(7):9748-9765.
  • 10. Polakis P. Wnt signaling in cancer. Cold Spring Harb Perspect Biol. 2012;4(5):a008052.
  • 11. Li F, Chong ZZ, Maiese K. Winding through the WNT pathway during cellular development and demise. Histol Histopathol 2006;21(1):103-124.
  • 12. Polakis P. Wnt signaling and cancer. Genes Dev 2000;14(15):1837-51.
  • 13. Kikuchi A. Regulation of beta-catenin signaling in the Wnt pathway. Biochem Biophys Res Commun 2000;268(2):243-8.
  • 14. Giles RH, van Es JH, Clevers H. Caught up in a Wnt storm: Wnt signaling in cancer. Biochim Biophys Acta 2003 Jun 5;1653(1):1-24.
  • 15. Lin J, Tan X, Qiu L, et al. Long Noncoding RNA BC032913 as a Novel Therapeutic Target for Colorectal Cancer that Suppresses Metastasis by Upregulating TIMP3. Mol Ther Nucleic Acids 2017;8:469-481.
  • 16. Ballantyne MD, McDonald RA, Baker AH. lncRNA/MicroRNA interactions in the vasculature. Clin Pharmacol Ther 2016;99(5):494-501.
  • 17. McMillan DC, Canna K, McArdle CS. Systemic inflammatoryresponse predicts survival following curative resection of col-orectal cancer. Br J Surg 2003;90:215-9.
  • 18. Skinner AC, Steiner MJ, Henderson FW, et al. Multiple markers of inflammation and weight status: cross-sectional analyses throughout childhood. Pediatrics. 2010; 125(4):e801-9.
  • 19. Fox P, Hudson M, Brown C, et al. Markers of systemic inflammation predict survival in patients with advanced renal cell cancer. Br J Cancer. 2013;109(1):147-53.
  • 20. Dai M, Chen X, Mo S, et al. Meta-signature LncRNAs serve as novel biomarkers for colorectal cancer: integrated bioinformatics analysis, experimental validation and diagnostic evaluation. Sci Rep 2017;7:46572.
  • 21. Arun G, Diermeier SD, Spector DL. Therapeutic Targeting of Long Non-Coding RNAs in Cancer. Trends Mol Med 2018;3:257-277.
  • 22. Qi SY, Riviere PJ, Trojnar J, et al. Cloning and characterization of dipeptidyl peptidase 10, a new member of an emerging subgroup of serine proteases. Biochem J 2003;373(Pt 1):179-89.
  • 23. Allen M, Heinzmann A, Noguchi E, et al. Positional cloning of a novel gene influencing asthma from chromosome 2q14. Nat Genet 2003;35:258-63.
  • 24. Park HS, Yeo HY, Chang HJ, et al. Dipeptidyl peptidase 10, a novel prognostic marker in colorectal cancer. Yonsei Med J 2013;54(6):1362-9.
  • 25. Gupta D, Lis CG. Pretreatment serum albumin as a predictor of cancer survival: a systematic review of the epidemiological literature. Nutr J 2010;9:69.
  • 26. Lu X, Guo W, Xu W, et al. Prognostic value of the Glasgow prognostic score in colorectal cancer: a meta-analysis of 9,839 patients. Cancer Manag Res. 2018;11:229-249.
  • 27. Shibutani M, Maeda K, Nagahara H, et al. The significance of the C-reactive protein to albumin ratio as a marker for predicting survival and monitoring chemotherapeutic effectiveness in patients with unresectable metastatic colorectal cancer. Springerplus 2016;5(1):1798.
  • 28. Tominaga T, Nonaka T, Sumida Yet al. The C-Reactive Protein to Albumin Ratio as a Predictor of Severe Side Effects of Adjuvant Chemotherapy in Stage III Colorectal Cancer Patients. PLoS One 2016;11(12):e0167967.
  • 29. Belau F, Metzner K, Christ T, et al. DPP10 is a new regulator of Nav1.5 channels in human heart. Int J Cardiol 2019;284:68-73.
  • 30. Roch AM, Parikh JA, Al-Haddad MA, et al. Abnormal serum pancreatic enzymes, but not pancreatitis, are associated with an increased risk of malignancy in patients with intraductal papillary mucinous neoplasms. Surgery. 2014;156(4):923-9.
  • 31. Date K, Yamazaki T, Toyoda Y, et al. α-Amylase expressed in human small intestinal epithelial cells is essential for cell proliferation and differentiation. J Cell Biochem 2020;121(2):1238-1249.
Toplam 31 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Sağlık Kurumları Yönetimi
Bölüm Makaleler
Yazarlar

Gülper Nacarkahya

Cem Horozoğlu 0000-0001-8998-2028

Proje Numarası TF.ALT.19.19
Yayımlanma Tarihi 11 Ocak 2022
Yayımlandığı Sayı Yıl 2020 Cilt: 20 Sayı: 3

Kaynak Göster

APA Nacarkahya, G., & Horozoğlu, C. (2022). Kolorektal kanserde lncRNA DPP10-AS1 ekspresyonu tümör baskılayıcı ve tümör mikroçevresinde metabolit transportuyla ilişkili olabilir mi?. Akademik Gastroenteroloji Dergisi, 20(3), 162-168. https://doi.org/10.17941/agd.974118

test-5