Significance of miR-148a in Colorectal Neoplasia: Downregulation of miR-148a Contributes to the Carcinogenesis and Cell Invasion of Colorectal Cancer

• Published in: Pathobiology (Basel) Vol. 82; no. 5; p. 233
• Main Authors: Hibino, Yumi, Sakamoto, Naoya, Naito, Yutaka, Goto, Keisuke, Oo, Htoo Zarni, Sentani, Kazuhiro, Hinoi, Takao, Ohdan, Hideki, Oue, Naohide, Yasui, Wataru
• Format: Journal Article
• Language: English
• Published: Switzerland 01-01-2015
• Subjects: Adult; Aged; Aged, 80 and over; Carcinogenesis - genetics; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; HT29 Cells; Humans; Male; Matrix Metalloproteinase 7 - genetics; MicroRNAs - genetics; Middle Aged; Neoplasm Invasiveness - genetics; Prognosis; Real-Time Polymerase Chain Reaction
• ISSN: 1423-0291
• DOI: 10.1159/000438826

Colorectal cancer (CRC) develops through the deregulation of gene expression and the accumulation of epigenetic abnormalities, leading to tumor cell acquisition of malignant features. MicroRNAs (miRNAs) play a critical role in cancer development, where they can act as oncogenes or oncosuppressors.
miR-148a expression was measured by qRT-PCR in patients with colorectal adenoma (n = 21) and CRC (stage I-IV, n = 159) using formalin-fixed paraffin-embedded tissue samples. In situ hybridization (ISH) using an miR-148a-specific probe was also performed. To further confirm the direct effect of miR-148a on matrix metalloproteinase (MMP)7 expression in CRC, MTT and cell invasion assays using HT29 and WiDr cells were performed.
miR-148a expression was found to be clearly downregulated in high-grade adenoma compared to low-grade adenoma on both qRT-PCR and ISH analysis. Downregulation of miR-148a expression was significantly correlated with advanced clinicopathological features and was an independent prognostic classifier in patients with stage III CRC. In CRC cells and tissues, miR-148a expression was inversely correlated with the expression of MMP7.
We showed the collaborative participation of miR-148a and MMP7 in CRC cell invasion. These results also demonstrate that the downregulation of miR-148a expression promotes CRC progression, especially carcinogenesis and cancer cell invasion.