The Cluster of miR-143 and miR-145 Affects the Risk for Esophageal Squamous Cell Carcinoma through Co-Regulating Fascin Homolog 1

Abstract

MicroRNAs (miRNAs), 18–24 nt non-coding RNAs, are thought to play important roles in cell proliferation, differentiation, apoptosis, and development. Recent studies suggest that some of the known microRNAs map to a single genomic locale within a single polycistronic transcript. But the roles of the cluster remain to be known. In order to understand the role and mechanism of a cluster of miR-143 and miR-145 in esophageal squamous cell carcinoma (ESCC), the association of mature miR-143 and miR-145 expression with the risk for esophageal cancer was evaluated in ESCC patients with a case-control study, and target protein regulated by mature miRNA was analyzed in ESCC cell lines with 3′UTR luciferase reporter assay. The expression levels of miR-143 and miR-145 were determined in 110 pairs of esophageal cancer tissues and adjacent normal tissues using real-time reverse transcription PCR. The relative expression of miR-143 and miR-145 were statistically different between cancer tissues and matched controls. The combined expression of miR-143 and miR-145 was significantly associated with the risk for esophageal cancer. Meanwhile, the reduced expression of two miRNAs in tumor patient was supposed to have a trend of lymph node metastases. The co-expression pattern of miR-143 and miR-145 was analyzed with Pearson correlation. It showed a significant correlation between these two miRNAs expression both in tissues and tumor cell lines. 3′UTR luciferase reporter assay indicated that Fascin Homolog 1 (FSCN1) could be co-regulated by miR-143 and miR-145. The protein level of FSCN1 showed no significant linear correlation with miR-143 and miR-145 expression in ESCC cell lines with Western blotting analysis. In conclusion, since miR-143 and miR-145 could regulate oncogenic FSCN1 and take part in the modulation of metastases, the result suggested the combination variable of miR-143 and miR-145 as a potential biomarker for earlier diagnosis and prognosis of esophageal cancer.

Identification of candidate target genes of genomic aberrations in esophageal squamous cell carcinoma

“…Hanker et al (18) observed that lower FSCN1 expression was associated with significantly poorer overall survival in epithelial ovarian cancer. In tumors, FSCN1 could be directly targeted and regulated by miR-133a, miR-133b, miR-143 and miR-145 (19)(20)(21)(22). Fuse et al (23) further revealed that restoration of miR-145 expression suppresses cell proliferation, migration and invasion in prostate cancer by targeting FSCN1.…”

A selective screening platform reveals unique global expression patterns of microRNAs in a cohort of human soft-tissue sarcomas

“…30), and affects the risk of esophageal squamous cell carcinoma through co-regulating fascin homolog 1. 31 MiR-145 is suppressed in renal cell carcinoma and targets metalloprotease ADAM17. 32 This miRNA is downregulated in glial tumors and regulates glioma cell migration by targeting connective tissue growth factor.…”

Double‐negative feedback loop between long non‐coding RNA TUG1 and miR‐145 promotes epithelial to mesenchymal transition and radioresistance in human bladder cancer cells

“…Results were normalized to the expression of U6 or GAPDH. The primers for TUG1 and miR-145 were previously described [6,7]. The primers for U6 were 5 0 -CTCGCTTCGGCAG CACA-3 0 (forward) and 5 0 -AACGCTTCACGAATTTGCGT-3 0 (reverse).…”