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

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Abstract

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.

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Abbreviations

CRC:

Colorectal cancer

lncRNA-CCHE1:

Cervical carcinoma high-expressed lncRNA 1

HOTAIR:

Hox transcript antisense intergenic RNA

MALAT1:

Metastasis-associated lung adenocarcinoma transcript 1

BANCR:

BRAF-activated non-protein coding RNA

HULC:

Highly upregulated in liver cancer

ERK1/2:

Extracellular signal regulated kinase1/2

COX-2:

Cyclooxygenase-2

PCNA:

Proliferating cell nuclear antigen

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Authors and Affiliations

  1. Medical Biochemistry Department, Faculty of Medicine,Tanta University, Tanta, Egypt

    Hanaa H. Gaballah & Rasha A. Gaber

  2. Histopathology Depatment, Faculty of medicine, Tanta University, Tanta, Egypt

    Mohamed A. Elrashidy

  3. Clinical Pathology Department, Faculty of Medicine, Tanta University, Tanta, Egypt

    Dina A. Elshahat

  4. General Surgery Department, Faculty of Medicine, Tanta University, Tanta, Egypt

    Mohamed A. Hablus

  5. Clinical Pharmacy Department, Faculty of Pharmacy, AL-Delta University, Gamasa, Egypt

    Abla M. Ebeid

Authors
  1. Hanaa H. Gaballah
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  2. Rasha A. Gaber
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  3. Mohamed A. Elrashidy
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  4. Dina A. Elshahat
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  5. Mohamed A. Hablus
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  6. Abla M. Ebeid
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Correspondence to Hanaa H. Gaballah.

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Gaballah, H.H., Gaber, R.A., Elrashidy, M.A. et al. Expression of long non-coding RNA CCHE1 in colorectal carcinoma: correlations with clinicopathological features and ERK/COX-2 pathway. Mol Biol Rep 46, 657–667 (2019). https://doi.org/10.1007/s11033-018-4521-0

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  • DOI: https://doi.org/10.1007/s11033-018-4521-0

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