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Role of miRNA-210, miRNA-21 and miRNA-126 as diagnostic biomarkers in colorectal carcinoma: impact of HIF-1α-VEGF signaling pathway

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Abstract

Colorectal cancer (CRC) is a major cause of death worldwide. Novel non-invasive, high diagnostic value screening test is urgently needed to improve survival rate, treatment and prognosis. Stable, small, circulating microRNA (miRNA) offers unique opportunities for the early diagnosis of several diseases. It acts as tumor oncogenes or suppressors and involve in cell death, survival, and metastasis. Communication between miRNA and carcinogenesis is critical but it still not clear and needs further investigation. The aim of our study is to evaluate the role of miR-210, miR-21, miR-126, as non-invasive diagnostic biomarkers for screening, early detection of CRC, studying their correlation with prognostic variables, and clarifying the roles of miRNAs on HIF-1α-VEGF signaling pathway. The expression of miR-210, miR-21 and miR-126 was performed using qRT-PCR in adenocarcinoma (no = 35), adenomas (no = 51), and neoplasm free controls (no = 101). Serum levels of VEGF and HIF-1α was determined by ELISA Kit. The results show that the expression of miR-210, miR-21, VEGF, HIF-1α was significantly up-regulated while that miRNA-126 was down-regulated in both adenocarcinoma and adenomas compared with controls (p < 0.001 for each). No significant difference was noted comparing patients with adenocarcinoma and adenomas. The three miRNAs correlated with VEGF, HIF-α. The miR-210 and miR-21 associated with TNM classification and clinical staging of adenocarcinoma (p < 0.001) and they show high diagnostic value with sensitivity and specificity 88.6%, 90.1% and 91.4%, 95.0% respectively. Our study revealed that circulating miR-210, miR-21 were up-regulated while miR-126 was down-regulated in CRC and adenomas patients, they all correlated with TNM staging and they had high diagnostic value. HIF-1α VEGF signaling pathways regulated by miRNAs played a role in colon cancer initiation. To the best of our knowledge, this is the first study of this miRNAs panel in CRC in our community. These data suggested that these biomarkers could be a potential novel, non-invasive marker for early diagnosis, screening and predicting prognosis of CRC. Understanding the molecular functions by which miRNAs affect cancer and understanding its roles in modulating the signaling output of VEGF might be fruitful in reducing the incidence and slowing the progression of this dark malignancy.

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Abbreviations

CRC:

Colorectal carcinoma

miR:

microRNA

qRT-PCR:

Quantitative real time polymerase chain reaction

VEGF:

Vascular endothelial growth factor

HIF-α:

Hypoxia inducible factor alpha

NF-kB:

Nuclear transcription factor

STAT3:

Signal transducer and activator of transcription 3

TNM stages:

Tumor-nodal-metastasis stages

PPV:

Positive predictive value

NPV:

Negative predictive value

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt

    Dina Sabry & Moataz Maher

  2. Medical Biochemistry Department, Faculty of Medicine, Assiut University, Assiut, Egypt

    Sahar E. M. El-Deek, Mona A. H. El-Baz & Hala M. El-Bader

  3. Biochemistry Department, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt

    Eman Amer

  4. Tropical Medicine Department, Faculty of Medicine, Assiut University, Assiut, Egypt

    Elham A. Hassan

  5. Tropical Medicine Department, Faculty of Medicine, Beny Suef University, Beny Suef, Egypt

    Wael Fathy

  6. Pathology Department, Faculty of Medicine, Assiut University, Assiut, Egypt

    Heba E. M. El-Deek

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  1. Dina Sabry
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  2. Sahar E. M. El-Deek
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Correspondence to Dina Sabry.

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Sabry, D., El-Deek, S.E.M., Maher, M. et al. Role of miRNA-210, miRNA-21 and miRNA-126 as diagnostic biomarkers in colorectal carcinoma: impact of HIF-1α-VEGF signaling pathway. Mol Cell Biochem 454, 177–189 (2019). https://doi.org/10.1007/s11010-018-3462-1

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