The functional significance of microRNA-375 in human squamous cell carcinoma: aberrant expression and effects on cancer pathways

Abstract

MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules consisting of 19-22 nucleotides that are involved in a variety of biological processes, including development, differentiation, apoptosis and cell proliferation. In cancer research, a growing body of evidence has indicated that miRNAs are aberrantly expressed in many types of human cancers and can function either as tumor suppressors or oncogenes. Bioinformatic predictions suggest that miRNAs regulate more than 30% of protein-coding genes. Aberrant expression of miRNAs in cancer cells causes destruction of miRNA-regulated messenger RNA networks. Therefore, the identification of miRNA-regulated cancer pathways is important for understanding the molecular mechanisms of human cancer. Searching for the aberrant expression of miRNAs in cancer cells is the first step in the functional analysis of miRNAs in cancer cells. Genome-wide miRNA expression signatures can rapidly and precisely reveal aberrant expression of miRNA in cancers. The miRNA expression signatures of human cancers have revealed that miR-375 is significantly downregulated in cancer cells. Our recent data on maxillary sinus, hypopharyngeal and esophageal squamous cell carcinomas have suggested that miR-375 is frequently downregulated and functions as a tumor suppressor that targets several oncogenic genes in cancer cells. In this review, we focus on several types of human squamous cell carcinoma and describe the aberrant expression of miRNAs and the cancer pathways they regulate in these diseases.

Regulation of MMP13 by antitumor microRNA-375 markedly inhibits cancer cell migration and invasion in esophageal squamous cell carcinoma

“…Thus, we found that loss of miR-375 expression enhanced cancer cell aggressiveness in ESCC. Many previous studies have shown that the expression of miR-375 is markedly decreased in several types of cancers and that miR-375 functions as an antitumor miRNA (15,24). In contrast to these antitumor activities, miR-375 is upregulated in pediatric acute myeloid leukemia (AML) and prostate cancer, suggesting that miR-375 acts as an oncogenic miRNA in these diseases (25,26).…”

“…Moreover, our previous studies demonstrated that ectopic expression of miR-375 suppressed cancer cell aggressiveness in several types of cancer cells (15). In ESCC cells, several studies have indicated that miR-375 has antitumor roles through targeting oncogenic genes (16,17).…”

Drug Resistance Mediated by AEG-1/MTDH/LYRIC

“…miR-375 was one of the most significantly downregulated microRNAs in that study. Dysregulated expression of miR-375 has also been detected in lung cancer, squamous cervical cancer, colon cancer and glioma (Bierkens et al, 2013; Chang et al, 2012; Dai et al, 2012; He et al, 2012; Isozaki et al, 2012; Kinoshita et al, 2012; Li et al, 2012b; Nohata et al, 2011; Ward et al, 2012). Interestingly, AEG-1/MTDH/LYRIC is a validated target of miR-375 (Ward et al, 2012).…”

The combined serum levels ofmiR-375and urokinase plasminogen activator receptor are suggested as diagnostic and prognostic biomarkers in prostate cancer

“…MiR‐375 has been described as downregulated in several tumor entities, such as tumors of the stomach, head and neck, esophagus, cervix, brain, colorectum and liver, in both primary tumor tissue and blood‐based fluids (reviewed in Ref. ]). It has been suggested that miR‐375 has tumor‐suppressive capabilities in several types of human squamous cell carcinomas .…”