Zhou Xiaoying, Ye Feng, Yin Chengqiang, Zhuang Ya, Yue Ge, Zhang Guoxin
Cell Physiol Biochem. 2015;36(4):1440-52. doi: 10.1159/000430309.
BACKGROUND/AIMS: Non-coding RNAs including miRNA and lncRNA had been reported to regulate gene expression and were both related to cancer progression. MicroRNA-141 (miR-141) has been reported to play a role in the epithelial to mesenchymal transition (EMT) process and H19 has also been demonstrated to promote malignancy in various cancers. We aimed to determine the correlation between miR-141 and H19 and their roles in gastric cancer in this study.
H19 and miR-141 expression were detected by qRT-PCR. By bioinformatic analysis and luciferase assay we examined the correlation between H19 and miR-141 in vitro.
H19 expression was found to be inversely correlated to miR-141 expression in gastric cancer cells and tissues. H19 promotes malignancy including proliferation and invasion whereas miR-141 suppresses malignancy in human cancer cells. MiR-141 binds to H19 in a sequence specific manner, and suppresses H19 expression and functions including proliferation and invasion. MiR-141 could also regulate H19 target genes and miR-141 inhibitor restores H19 siRNA function, while H19 regulates miR-141 target gene ZEB1.
These results were the first to demonstrate that H19 and miR-141 could compete with each other and affect their target genes in gastric cancer, which provide important clues for understanding the key roles of lncRNA-miRNA functional network in cancer.
背景/目的:据报道,包括miRNA和lncRNA在内的非编码RNA可调节基因表达,且均与癌症进展相关。据报道,微小RNA-141(miR-141)在上皮-间质转化(EMT)过程中发挥作用,H19也已被证明可促进多种癌症的恶性进展。在本研究中,我们旨在确定miR-141与H19之间的相关性及其在胃癌中的作用。
采用qRT-PCR检测H19和miR-141的表达。通过生物信息学分析和荧光素酶报告基因检测,我们在体外研究了H19与miR-141之间的相关性。
发现H19的表达与胃癌细胞和组织中miR-141的表达呈负相关。H19促进包括增殖和侵袭在内的恶性进展,而miR-141抑制人类癌细胞的恶性进展。MiR-141以序列特异性方式与H19结合,并抑制H19的表达及其包括增殖和侵袭在内的功能。MiR-141还可调节H19的靶基因,miR-141抑制剂可恢复H19 siRNA的功能,而H19调节miR-141的靶基因ZEB1。
这些结果首次证明H19和miR-141在胃癌中可相互竞争并影响其靶基因,这为理解lncRNA-miRNA功能网络在癌症中的关键作用提供了重要线索。