食道扁平上皮がんにおけるmicroRNA-210の機能と役割

抄録

  In this review, we summarize our findings on microRNA-210 (miR-210) and the target gene, and discuss their significance in human esophageal squamous cell carcinoma (ESCC). MicroRNAs are evolutionarily conserved small noncoding RNAs (20-23 nucleotides) that bind to complementary sequences in the 3′ UTR of target mRNAs and regulate gene expression by the cleavage of target mRNAs and/or translational inhibition. MicroRNAs play important roles in the initiation and progression of cancer, and it has been shown that the expression of some microRNAs is altered in malignancies. Carcinomas are derived from epithelial cells, and poor prognosis in patients with carcinoma is associated with the disruption of characteristics of differentiated epithelial cells, such as cell junctions and polarity. Here, we identified miR-210 as one of the microRNAs that is markedly differentially expressed during the process of epithelial differentiation, though the clinical roles of miR-210 in carcinomas remained unknown. We show that the expression of miR-210 is downregulated in ESCC and derived cell lines. Marked decreases in the level of miR-210 were observed especially in poorly differentiated carcinomas. Moreover, we found that miR-210 inhibits cancer cell survival and proliferation. Finally, we identified fibroblast growth factor receptor-like 1 (FGFRL1) as a target gene of miR-210 in ESCC, and demonstrated that FGFRL1 accelerates cancer cell proliferation. Taken together, our findings show an important role for miR-210 as a tumor suppressive microRNA with effects on cancer cell proliferation.