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.