Identification and functional screening of microRNAs highly deregulated in colorectal cancer

Abstract

MicroRNAs (miRNAs) constitute a robust regulatory network with post-transcriptional regulatory efficiency for almost one half of human coding genes, including oncogenes and tumour suppressors. We determined the expression profile of 667 miRNAs in colorectal cancer (CRC) tissues and paired non-tumoural tissues and identified 42 differentially expressed miRNAs. We chose miR-215, miR-375, miR-378, miR-422a and miR-135b for further validation on an independent cohort of 125 clinically characterized CRC patients and for in vitro analyses. MiR-215, miR-375, miR-378 and miR-422a were significantly decreased, whereas miR-135b was increased in CRC tumour tissues. Levels of miR-215 and miR-422a correlated with clinical stage. MiR-135b was associated with higher pre-operative serum levels of CEA and CA19-9. In vitro analyses showed that ectopic expression of miR-215 decreases viability and migration, increases apoptosis and promotes cell cycle arrest in DLD-1 and HCT-116 colon cancer cell lines. Similarly, overexpression of miR-375 and inhibition of miR-135b led to decreased viability. Finally, restoration of miR-378, miR-422a and miR-375 inhibited G1/S transition. These findings indicate that miR-378, miR-375, miR-422a and miR-215 play an important role in CRC as tumour suppressors, whereas miR-135b functions as an oncogene; both groups of miRNA contribute to CRC pathogenesis.

Identification and characterization of tumor suppressor and oncogenic miRNAs in gastric cancer

“…Alternative studies have demonstrated that miR-215 downregulates thymidylate synthetase, dihydrofolate reductase, thymidylate synthetase and denticleless E3 ubiquitin protein ligase homolog, and functions in the development of chemotherapy resistance (33,34). Furthermore, the upregulation of miR-215 was observed in esophageal, kidney and colon cancer (35)(36)(37). In contrast to its role in other solid tumors, miR-215 functions as an oncogene in gastric cancer by promoting cell proliferation and cancer cell metastasis (38-40); however, the underlying mechanism has yet to be defined.…”

miR-155 as a diagnostic and prognostic marker in hematological and solid malignancies

“…Overexpression or downregulation of a subset of miRNAs have also been described in colorectal cancer and potential role of miR-155 was suggested too [86,87]. In CRC, mir-135b is the most abundantly overexpressed miRNA.…”

ReducedmiR-215expression predicts poor prognosis in patients with acute myeloid leukemia

“…Previous studies showed that miR-215 could act as a tumor suppressor gene, and down-regulation of miR-215 was identified in several cancers, such as myeloma (14), nephroblastoma (15), esophageal adenocarcinoma (16), breast cancer (BC) (17) and colon cancer (18,19). However, the status of miR-215 expression and its prognostic value remain unclear in AML.…”