Molecular Biology Reports

, Volume 46, Issue 1, pp 657–667 | Cite as

Expression of long non-coding RNA CCHE1 in colorectal carcinoma: correlations with clinicopathological features and ERK/COX-2 pathway

  • Hanaa H. GaballahEmail author
  • Rasha A. Gaber
  • Mohamed A. Elrashidy
  • Dina A. Elshahat
  • Mohamed A. Hablus
  • Abla M. Ebeid
Original Article


Colorectal cancer (CRC) is among the leading causes of cancer-related mortality worldwide. Compelling evidence suggests that long non-coding RNA (lncRNAs) can control carcinogenesis by regulating various aspects of cell biology. However, limited number of CRC-related lncRNAs has been well characterized. This study was undertaken to investigate the expression pattern of the novel lncRNA-CCHE1 in CRC patients and to examine its correlation with clinicopathological features, ERK/COX-2 pathway and some cell proliferation markers in order to gain biological insights on its role in CRC pathogenesis. Colon cancer specimens with their adjacent non-cancerous tissues were taken from 60 patients with primary CRC. LncRNA-CCHE1 relative expression was assessed using quantitative real-time RT-PCR. P-ERK ½ and cyclin D1 levels were estimated by ELISA. COX-2 and proliferating cell nuclear antigen (PCNA) expression were assessed immunohistochemically. lncRNA-CCHE1 expression was upregulated in CRC tissues compared to adjacent non-cancerous tissues, and was significantly associated with larger tumor size, less differentiated histology, advanced dukes’ stage, positive lymph node involvement and vascular invasion. It also showed a significant positive correlation with the expression of p-ERK1/2, COX-2 as well as cyclin D1and PCNA (as markers for cell proliferation). These findings signify that lncRNA-CCHE1 is a key oncogene possibly involved in CRC development and progression by modulating ERK/COX-2 pathway and cell proliferation activity. Our study also provides a rationale for potential use of lncRNA-CCHE1 as a novel prognostic marker, and opens the door for the development of lncRNA-CCHE1-directed therapeutic approaches for CRC patients.


Colorectal carcinoma Long non-coding RNA CCHE1 ERK1/2 Cyclin D1 COX-2 PCNA 



Colorectal cancer


Cervical carcinoma high-expressed lncRNA 1


Hox transcript antisense intergenic RNA


Metastasis-associated lung adenocarcinoma transcript 1


BRAF-activated non-protein coding RNA


Highly upregulated in liver cancer


Extracellular signal regulated kinase1/2




Proliferating cell nuclear antigen


Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.


  1. 1.
    Siegel RL et al (2017) Colorectal cancer statistics, 2017. CA Cancer J Clin 67(3):177–193CrossRefGoogle Scholar
  2. 2.
    Tariq K, Ghias K (2016) Colorectal cancer carcinogenesis: a review of mechanisms. Cancer Biol Med 13(1):120CrossRefGoogle Scholar
  3. 3.
    Schmitt AM, Chang HY (2016) Long noncoding RNAs in cancer pathways. Cancer Cell 29(4):452–463CrossRefGoogle Scholar
  4. 4.
    Kashi K et al (2016) Discovery and functional analysis of lncRNAs: methodologies to investigate an uncharacterized transcriptome. Biochim Biophys Acta 1859(1):3–15CrossRefGoogle Scholar
  5. 5.
    Xie X et al (2016) Long non-coding RNAs in colorectal cancer. Oncotarget 7(5):5226–5239CrossRefGoogle Scholar
  6. 6.
    Ragusa M et al (2015) Non-coding landscapes of colorectal cancer. World J Gastroenterol 21(41):11709–11739CrossRefGoogle Scholar
  7. 7.
    Deng H et al (2017) Long non-coding RNAs: new biomarkers for prognosis and diagnosis of colon cancer. Tumor Biol 39(6):1010428317706332CrossRefGoogle Scholar
  8. 8.
    Yang M et al (2015) Long noncoding RNA CCHE1 promotes cervical cancer cell proliferation via upregulating PCNA. Tumor Biol 36(10):7615–7622CrossRefGoogle Scholar
  9. 9.
    Liu B, Qu L, Yan S (2015) Cyclooxygenase-2 promotes tumor growth and suppresses tumor immunity. Cancer Cell Int 15(1):106CrossRefGoogle Scholar
  10. 10.
    Bhattacharyya S et al (2016), Tenascin-C drives persistence of organ fibrosis. Nat Commun 7:11703CrossRefGoogle Scholar
  11. 11.
    Sun Y et al (2015) Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis. J Recept Signal Transduct 35(6):600–604CrossRefGoogle Scholar
  12. 12.
    Lim S, Kaldis P (2013) Cdks, cyclins and CKIs: roles beyond cell cycle regulation. Development 140(15):3079–3093CrossRefGoogle Scholar
  13. 13.
    Xu MD, Qi P, Du X (2014) Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application. Mod Pathol 27(10):1310–1320CrossRefGoogle Scholar
  14. 14.
    Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72(1–2):248–254CrossRefGoogle Scholar
  15. 15.
    Zhan Y et al (2017) Increased expression of long non-coding RNA CCEPR is associated with poor prognosis and promotes tumorigenesis in urothelial bladder carcinoma. Oncotarget 8(27):44326–44334CrossRefGoogle Scholar
  16. 16.
    Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2 – ∆∆CT method. Methods 25(4):402–408CrossRefGoogle Scholar
  17. 17.
    Broders AC (1925) The grading of carcinoma. Minn Med 8(726):1730–1925Google Scholar
  18. 18.
    Dukes CE (1949) The surgical pathology of rectal cancer. J Clin Pathol 2(2):95–98CrossRefGoogle Scholar
  19. 19.
    Remmele W, Stegner HE (1987) Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe 8(3):138–140Google Scholar
  20. 20.
    Sun XF et al (1996) Proliferating cell nuclear antigen (PCNA) in relation to ras, c-erbB-2,p53, clinico-pathological variables and prognosis in colorectal adenocarcinoma. Int J Cancer 69(1):5–8CrossRefGoogle Scholar
  21. 21.
    Grady WM, Markowitz SD (2015) The molecular pathogenesis of colorectal cancer and its potential application to colorectal cancer screening. Dig Dis Sci 60(3):762–772CrossRefGoogle Scholar
  22. 22.
    Peng W, Fan H (2016) Long noncoding RNA CCHE1 indicates a poor prognosis of hepatocellular carcinoma and promotes carcinogenesis via activation of the ERK/MAPK pathway. Biomed Pharmacother 83:450–455CrossRefGoogle Scholar
  23. 23.
    Chen Y et al (2017) Long non-coding RNA CCHE1 overexpression predicts a poor prognosis for cervical cancer. Eur Rev Med Pharmacol Sci 21(3):479–483Google Scholar
  24. 24.
    Xu G et al (2018) LncRNA CCHE1 in the proliferation and apoptosis of gastric cancer cells. Eur Rev Med Pharmacol Sci 22(9):2631–2637Google Scholar
  25. 25.
    Liao Y et al (2018) lncRNA CCHE1 increased proliferation, metastasis and invasion of non-small lung cancer cells and predicted poor survival in non-small lung cancer patients. Eur Rev Med Pharmacol Sci 22(6):1686–1692Google Scholar
  26. 26.
    Scrima M et al (2017) Aberrant signaling through the HER2-ERK1/2 pathway is predictive of reduced disease-free and overall survival in early stage non-small cell lung cancer (NSCLC) patients. J Cancer 8(2):227CrossRefGoogle Scholar
  27. 27.
    Bai L et al (2015) ERK1/2 promoted proliferation and inhibited apoptosis of human cervical cancer cells and regulated the expression of c-Fos and c-Jun proteins. Med Oncol 32(3):57CrossRefGoogle Scholar
  28. 28.
    Zhao L et al (2015) Benzidine induces epithelial-mesenchymal transition in human uroepithelial cells through ERK1/2 pathway. Biochem Biophys Res Commun 459(4):643–649CrossRefGoogle Scholar
  29. 29.
    Ding G et al (2015) Over-expression of lipocalin 2 promotes cell migration and invasion through activating ERK signaling to increase SLUG expression in prostate cancer. Prostate 75(9):957–968CrossRefGoogle Scholar
  30. 30.
    Elzagheid A et al (2013) High cyclooxygenase-2 expression is associated with advanced stages in colorectal cancer. Anticancer Res 33(8):3137–3143Google Scholar
  31. 31.
    Wu QB, Sun GP (2015) Expression of COX-2 and HER-2 in colorectal cancer and their correlation. World J Gastroenterol 21(20):6206–6214CrossRefGoogle Scholar
  32. 32.
    Rizzo MT (2011) Cyclooxygenase-2 in oncogenesis. Clin Chim Acta 412(9–10):671–687CrossRefGoogle Scholar
  33. 33.
    Barnum KJ, O’Connell MJ (2014) Cell cycle regulation by checkpoints. Cell Cycle Control 1170:29–40Google Scholar
  34. 34.
    Qie S, Diehl JA (2016) Cyclin D1, cancer progression, and opportunities in cancer treatment. J Mol Med 94(12):1313–1326CrossRefGoogle Scholar
  35. 35.
    Li Y et al (2014) Prognostic significance of cyclin D1 expression in colorectal cancer: a meta-analysis of observational studies. PLoS ONE 9(4):e94508CrossRefGoogle Scholar
  36. 36.
    Wang HY et al (2014) HBx protein promotes oval cell proliferation by up-regulation of cyclin D1 via activation of the MEK/ERK and PI3K/Akt pathways. Int J Mol Sci 15(3):3507–3518CrossRefGoogle Scholar
  37. 37.
    Han DP et al (2012) Polo-like kinase 1 is overexpressed in colorectal cancer and participates in the migration and invasion of colorectal cancer cells. Med Sci Monit 18(6):Br237–B46CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  • Hanaa H. Gaballah
    • 1
    Email author
  • Rasha A. Gaber
    • 1
  • Mohamed A. Elrashidy
    • 2
  • Dina A. Elshahat
    • 3
  • Mohamed A. Hablus
    • 4
  • Abla M. Ebeid
    • 5
  1. 1.Medical Biochemistry DepartmentFaculty of Medicine,Tanta UniversityTantaEgypt
  2. 2.Histopathology DepatmentFaculty of medicine, Tanta UniversityTantaEgypt
  3. 3.Clinical Pathology DepartmentFaculty of Medicine, Tanta UniversityTantaEgypt
  4. 4.General Surgery Department, Faculty of MedicineTanta UniversityTantaEgypt
  5. 5.Clinical Pharmacy Department, Faculty of PharmacyAL-Delta UniversityGamasaEgypt

Personalised recommendations